Regulation of Early Eye Development in the Developing Chick Embryo

PD Dr. Astrid Vogel-Höpker

The goal of our research is to elucidate the cellular and molecular mechanisms that regulate the patterning and differentiation of ocular tissues, specifically the neural retina and retinal pigmentepithelium.

Regulation of Early Eye Development in the Developing Chick Embryo

Picture: Astrid Vogel-Höpker

Vertebrate eye development is initiated through the evagination of the optic vesicle of the forebrain. These neuroepithelial cells of the optic vesicle are initially indistinguishable, coexpressing a number of transcription factors and these cells are competent to develop into the multilayered neural retina (NR), the single-layered retinal pigment epithelium (RPE) and optic stalk. The development of the eye is the result of a complex, reciprocal interaction between several tissues.

Extrinsic signals released from the surrounding tissues appear to induce and repress specific transcription factors which eventually subdivide the optic vesicle into a NR and RPE domain. In order to identify signaling molecules and to characterize their in vivo role we use a combination of molecular, cellular and embryological approaches. Using the developing chick embryo, it is possible to bring together well-established embryological manipulations with genetic manipulations, such as mis- and overexpression of genes and gene inactivation. Importantly, such manipulations can be precisely targeted in time and space to dissect out the individual functions of these signals that play multiple roles during closely spaced time points of eye development. We have previously identified members of the Bone morphogenetic Protein- (BMP) and Fibroblast Growth Factor- (FGF) family as important signals being involved in NR and RPE development, respectively. For example, application of FGF8-soaked beads during early stages of chick eye development respecifies the single layered pigmented RPE to develop into a second multilayered NR. In contrast, ectopic BMP-application induces the presumptive NR to develop into RPE.

Identifying the cellular and molecular mechanisms that act endogenously in eye formation will significantly increase our understanding of vertebrate embryology in general and of eye development in particular, as these key extracellular signaling factors may be used to direct human embryonic stem cell differentiation into RPE and NR. These results potentially provide the basis for the development of novel therapeutical ap-proaches for the treatment of major blinding diseases, such as retinitis pigmentosa, aged-related macular degeneration and diabetic retinopathy.

Vertebrate limb development

We are interested in understanding the celluar and molecular signals that direct growth and patterning of the vertebrate limb. Initially the limb forms through the continued proliferation of the body wall mesenchyme at the level of the future fore- and hindlimb region. The mesenchyme then induces the overlying ectoderm to thicken to form a specialised epithelial structure at the tip of the bud, the so called apical ectodermal ridge (AER). The chick wing then continues to grow and eventually develops into a humerus, radius, ulna and digit2 and the posterior digits 3 and 4.

Our laboratory is interested in finding out the mechanisms that ensure that the structures of the limb, such as bones and muscles, develop in their proper positions. For example, how is it that a thumb develops at one edge of our hand and a little finger at the other. We have been involved in the identification of signalling molecules that are important regulators during vertebrate limb development. Interestingly, some of the genes already identified are responsible for limb defects in human patients or are involved in formation of tumours. Currently, we are trying to elucidate possible functions of the cholinergic system during cartilage, bone and muscle formation in the limb (see Layer, 1990; Alber et al., 1994) by carrying out gain- and loss-of-function studies in the chick and analysing single and double knock-out mutants in mice. The discovery of developmentally important genes may suggest new approaches to repair and regenerate limb tissues.

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Number of items: 14.


Spieker, Janine ; Frieß, Johannes L. ; Sperling, Laura ; Thangaraj, Gopenath ; Vogel-Höpker, A. ; Layer, Paul G. (2020):
Cholinergic control of bone development and beyond.
In: International immunopharmacology, 83, p. 106405. ISSN 1878-1705,
DOI: 10.1016/j.intimp.2020.106405,


Shirahama, Misaki ; Steinfeld, Ichie ; Karaiwa, Akari ; Taketani, Shigeru ; Vogel-Höpker, A. ; Layer, Paul G. ; Araki, Masasuke (2019):
Change in the developmental fate of the chick optic vesicle from the neural retina to the telencephalon.
In: Development, Growth & Differentiation, 61 (3), pp. 252-262. ISSN 0012-1592,
DOI: 10.1111/dgd.12599,


Steinfeld, Jörg ; Steinfeld, Ichie ; Bausch, Alexander ; Coronato, Nicola ; Hampel, Meggi-Lee ; Depner, Heike ; Layer, Paul G. ; Vogel-Höpker, A. (2017):
BMP-induced reprogramming of the neural retina into retinal pigment epithelium requires Wnt signalling.
In: Biology open, 6 (7), pp. 979-992. [Article]

Spieker, Janine ; Mudersbach, Thomas ; Vogel-Höpker, A. ; Layer, Paul G. (2017):
Endochondral Ossification Is Accelerated in Cholinesterase-Deficient Mice and in Avian Mesenchymal Micromass Cultures.
In: PloS one, 12 (1), ISSN 1932-6203,
DOI: 10.1371/journal.pone.0170252,


Spieker, Janine ; Ackermann, Anica ; Salfelder, Anika ; Vogel-Höpker, A. ; Layer, Paul G. (2016):
Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms.
In: PloS one, 11 (8), pp. e0161675. ISSN 1932-6203,


Steinfeld, Jörg ; Steinfeld, Ichie ; Coronato, Nicola ; Hampel, Meggi-Lee ; Layer, Paul G. ; Araki, Masasuke ; Vogel-Höpker, A. (2013):
RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling.
In: Development (Cambridge, England), 140 (24), pp. 4959-69. ISSN 1477-9129,

Layer, Paul G. ; Klaczinski, Janine ; Salfelder, Anika ; Sperling, Laura E. ; Thangaraj, Gopenath ; Tuschl, Corina ; Vogel-Höpker, A. (2013):
Cholinesterases in development: AChE as a firewall to inhibit cell proliferation and support differentiation.
In: Chemico-biological interactions, 203 (1), pp. 269-276. ISSN 1872-7786,

Layer, Paul G. ; Klaczinski, Janine ; Vogel-Höpker, A. ; Thangaraj, Gopenath (2013):
Developmental cholinergic mechanism : Do not forget the colinesterases!
In: Autonomic neuroscience : basic and clinical, 177, pp. 1-65. [Article]


Vogel-Höpker, A. ; Sperling, Laura E. ; Layer, Paul G. (2012):
Co-opting functions of cholinesterases in neural, limb and stem cell development.
In: Protein and peptide letters, 19 (2), pp. 155-164. ISSN 1875-5305,


Layer, Paul G. ; Araki, Masasuke ; Vogel-Höpker, A. (2010):
New concepts for reconstruction of retinal and pigment epithelial tissues.
In: Expert Review of Ophthalmology, 5 (4), pp. 523-543. [Article]


Müller, F. ; Rohrer, H. ; Vogel-Höpker, A. (2007):
Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo.
In: Development (Cambridge, England), 134 (19), pp. 3483-93. ISSN 0950-1991,


Vogel-Höpker, A. ; Rohrer, H. (2002):
The specification of noradrenergic locus coeruleus (LC) neurones depends on bone morphogenetic proteins (BMPs).
In: Development (Cambridge, England), 129 (4), pp. 983-91. ISSN 0950-1991,


Vogel-Höpker, A. ; Momose, T. ; Rohrer, H. ; Yasuda, K. ; Ishihara, L. ; Rapaport, D. H. (2000):
Multiple functions of fibroblast growth factor-8 (FGF-8) in chick eye development.
In: Mechanisms of development, 94 (1-2), pp. 25-36. ISSN 0925-4773,


Takeuchi, J. K. ; Koshiba-Takeuchi, K. ; Matsumoto, K. ; Vogel-Höpker, A. ; Naitoh-Matsuo, M. ; Ogura, K. ; Takahashi, N. ; Yasuda, K. ; Ogura, T. (1999):
Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds.
In: Nature, 398 (6730), pp. 810-4. ISSN 0028-0836,

This list was generated on Fri Sep 17 03:46:14 2021 CEST.
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Number of items: 13.


Müntinga, H. ; Ahlers, Holger ; Krutzik, M. ; Wenzlawski, A. ; Arnold, S. ; Becker, D. ; Bongs, Kai ; Dittus, H. ; Duncker, H. ; Gaaloul, Naceur ; Gherasim, Christina ; Giese, Enno ; Grzeschik, C. ; Hänsch, T.W. ; Hellmig, O. ; Herr, W. ; Herrmann, S. ; Kajari, E. ; Kleinert, S. ; Lämmerzahl, Claus ; Lewoczko-Adamczyk, W. ; Malcolm, J. ; Meyer, N. ; Nolte, Roman ; Peters, A. ; Popp, M. ; Reichel, J. ; Roura, A. ; Rudolph, J. ; Schiemangk, M. ; Schneider, Mathias ; Seidel, S.T. ; Sengstock, K. ; Tamma, V. ; Valenzuela, T. ; Vogel, A. ; Walser, Reinhold ; Wendrich, T. ; Windpassinger, Patrick ; Zeller, W. ; van Zoest, T. ; Ertmer, W. ; Schleich, Wolfgang P. ; Rasel, Ernst M. (2013):
Interferometry with Bose-Einstein Condensates in Microgravity.
In: Physical Review Letters, 110 (9), APS Physics, ISSN 0031-9007,
DOI: 10.1103/PhysRevLett.110.093602,


van Zoest, T. ; Gaaloul, Naceur ; Singh, Y. ; Ahlers, H. ; Herr, W. ; Seidel, S. T. ; Ertmer, Wolfgang ; Rasel, Ernst M. ; Eckart, M. ; Kajari, E. ; Arnold, S. ; Nandi, G. ; Schleich, Wolfgang P. ; Walser, Reinhold ; Vogel, A. ; Sengstock, K. ; Bongs, Kai ; Lewoczko-Adamczyk, W. ; Schiemangk, M. ; Schuldt, T. ; Peters, A. ; Könemann, T. ; Müntinga, H. ; Lämmerzahl, C. ; Dittus, H. ; Steinmetz, T. ; Hänsch, T.W. ; Reichel, J. (2010):
Bose-Einstein Condensation in Microgravity.
In: Science, 328 (5985), pp. 1540-1543. AAAS, ISSN 1095-9203,
DOI: 10.1126/science.1189164,


van Zoest, T. ; Müller, T. ; Wendrich, T. ; Gilowski, M. ; Rasel, Ernst M. ; Ertmer, Wolfgang ; Könemann, T. ; Lämmerzahl, Claus ; Dittus, Hansjörg ; Vogel, A. ; Bongs, Kai ; Sengstock, K. ; Lewoczko, W. ; Peters, A. ; Steinmetz, T. ; Reichel, J. ; Nandi, G. ; Schleich, Wolfgang P. ; Walser, Reinhold (2007):
Atomic Quantum Sensors in Space.
In: International Journal of Modern Physics D, 16 (12b), pp. 2421-2429. ISSN 0218-2718,
DOI: 10.1142/S0218271807011358,

Könemann, T. ; Brinkmann, W. ; Göklü, E. ; Lämmerzahl, Claus ; Dittus, H. ; van Zoest, Tim ; Rasel, Ernst M. ; Ertmer, Wolfgang ; Lewoczko-Adamczyk, W. ; Schiemangk, M. ; Peters, A. ; Vogel, A. ; Johannsen, G. ; Wildfang, S. ; Bongs, Kai ; Sengstock, K. ; Kajari, Endre ; Nandi, G. ; Walser, Reinhold ; Schleich, Wolfgang P. (2007):
A freely falling magneto-optical trap drop tower experiment.
In: Applied Physics B, 89 (4), pp. 431-438. Springer Nature, ISSN 0946-2171,
DOI: 10.1007/s00340-007-2863-8,


Vogel, A. ; Schmidt, M. ; Sengstock, K. ; Bongs, Kai ; Lewoczko-Adamczyk, W. ; Schuldt, T. ; Peters, A. ; van Zoest, T. ; Ertmer, W. ; Rasel, Ernst M. ; Steinmetz, T. ; Reichel, J. ; Könemann, T. ; Brinkmann, W. ; Göklü, E. ; Lämmerzahl, Claus ; Dittus, Hansjörg ; Nandi, G. ; Schleich, Wolfgang P. ; Walser, Reinhold (2006):
Bose-Einstein condensates in microgravity.
In: Applied Physics B, 84 (4), pp. 663-671. Springer Nature, ISSN 0946-2171,
DOI: 10.1007/s00340-006-2359-y,


Vogel, A. ; Rodriguez, C. ; Izpisúa-Belmonte, J. C. (1996):
Involvement of FGF-8 in initiation, outgrowth and patterning of the vertebrate limb.
In: Development (Cambridge, England), 122 (6), pp. 1737-50. ISSN 0950-1991,

Ogura, T. ; Alvarez, I. S. ; Vogel, A. ; Rodríguez, C. ; Evans, R. M. ; Izpisúa Belmonte, J. C. (1996):
Evidence that Shh cooperates with a retinoic acid inducible co-factor to establish ZPA-like activity.
In: Development (Cambridge, England), 122 (2), pp. 537-42. ISSN 0950-1991,

Kostakopoulou, K. ; Vogel, A. ; Brickell, P. ; Tickle, C. (1996):
'Regeneration' of wing bud stumps of chick embryos and reactivation of Msx-1 and Shh expression in response to FGF-4 and ridge signals.
In: Mechanisms of development, 55 (2), pp. 119-31. ISSN 0925-4773,


Vogel, A. ; Rodriguez, C. ; Warnken, W. ; Izpisúa Belmonte, J. C. (1995):
Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.
In: Nature, 378 (6558), pp. 716-20. ISSN 0028-0836,

Vogel, A. ; Roberts-Clarke, D. ; Niswander, L. (1995):
Effect of FGF on gene expression in chick limb bud cells in vivo and in vitro.
In: Developmental biology, 171 (2), pp. 507-20. ISSN 0012-1606,


Niswander, L. ; Tickle, C. ; Vogel, A. ; Martin, G. (1994):
Function of FGF-4 in limb development.
In: Molecular reproduction and development, 39 (1), pp. 83-8; discussion 88. ISSN 1040-452X,


Niswander, L. ; Tickle, C. ; Vogel, A. ; Booth, I. ; Martin, G. R. (1993):
FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb.
In: Cell, 75 (3), pp. 579-87. ISSN 0092-8674,

Vogel, A. ; Tickle, C. (1993):
FGF-4 maintains polarizing activity of posterior limb bud cells in vivo and in vitro.
In: Development (Cambridge, England), 119 (1), pp. 199-206. ISSN 0950-1991,

This list was generated on Fri Sep 17 08:01:50 2021 CEST.