Developmental Biology and Neurogenetics
Prof. Dr. Paul G. Layer

What is Developmental Biology?

Developmental Biology analyses highly integrated feedback processes at molecular, cellular and histological levels, which direct the entire development from fertilisation of the egg through maturation of the adult organism. As systems of study, we use appropriate model embryos, e.g. from chicken, zebrafish or mouse.

This knowledge is ground-breaking for all biomedical progress (e.g. stem cell biology, regenerative medicine, cancer research), as well as for a better understanding of evolution. In this group, we investigate molecular and cellular processes of development of the eyes (retina), the brain, or limbs. Thereby, acetylcholine and its protein components (e.g. cholinesterases) play a central role.

What is Neurogenetics?

Neurogenetics as part of developmental biology investigates molecular bases of the embryonic formation of nervous systems. A general question is, how a huge number of specific neuronal connections as required for a functional brain (1016/person) can be established, given that the total number of genes in man is very limited (2x104/person). Thereby, we analyse roles of acetylcholine and various growth factors.

Due to its simple layered structure, we focus on the development of the vertebrate retina in eyes from chicken and mouse embryos. Our cell biological techniques also allow us to culture artificial retinal tissues from stem cells (e.g. retinal spheroids), as well as develop methods for replacement of animal experiments.

Acetylcholinesterase (AChE) degrading the neurotransmitter acetylcholine (ACh) is a most remarkable protein, not only because it is one of the fastest enzymes in nature, but also since it appears in many molecular forms and is regulated by elaborate genetic networks. Moreover, specific inhibitors of cholinesterase (ChEs) play major roles in everyday life as medical therapeutics, as pesticides in agriculture and households, and as chemical warfare agents (nerve gases).

As revealed by sensitive histochemical procedures, AChE is expressed specifically in many tissues during development and in many mature organisms, as well as in healthy and diseased states. Therefore it is not surprising that there has been a long-standing search for additional, “non-classical” functions of cholinesterases (ChEs). In principle, AChE could either act non-enzymatically, e.g. exerting cell adhesive roles, or, alternatively, it could work within the frame of classic cholinergic systems, but in non-neural tissues. AChE might be considered a highly co-opting protein, since possibly it combines such various functions within one molecule.

Our research into ChEs functioning has focused upon i) the expression of ChEs in the neural tube and their close relation to cell proliferation and differentiation, ii) that AChE expression reflects a polycentric brain development, iii) the retina as a model for AChE functioning in neural network formation, and iv) non-neural ChEs in limb development and mature bones. Also, possible roles of AChE in neuritic growth and of cholinergic regulations in stem cells.

AChE functions in proper formation of the mouse retina. An AChE knockout mouse (right) presents disturbed sublayer formation of the inner plexiform layer (IPL; a synaptic layer). Staining: calretinin. Details in Bytyqi et al. 2004.

Possible schemes of developmental actions of ACh and AChE in neurite growth, cell contact formation and cell signaling. (a) secreted ACh from growth cone stops its further advancement („deceleration“). (b) approaching an AChE+ target cell, secreted ACh is degraded and growth cone is further attracted („attraction“), (c) „adhesion“ between two cells could be further stabilised by heterotypic interaction of ChED proteins (e.g. neuroligins, AChE) with neurexins. (d) Alternatively, AChE can bind to laminin of the ECM, which in turn can bind to integrin-2, enabling „adhesion“ and „signaling“ into cell interior. Further see Vogel-Höpker et al. 2010

The highly ordered organisation of cell types within distinct cell layers is a typical feature of many areas of vertebrate brains, representing a necessary requisite of functional neuronal networks. We study the formation of cell layers both in vivo and in vitro, by using as model systems retinae from chick embryos and neonatal rodents.

As our major in vitro approach, we take advantage of so called retinal spheroids, e.g. the cellular reconstruction of more or less complete 3-dimensional retinal tissue spheres from fully dispersed cells. This technology enables us to define the requirements and constraints of the formation of retinal tissues by a cell-to-cell reaggregation analysis. Noticeably, spheres are fully amenable for molecular intervention towards specific aspects of retinal differentiation, e.g. by use of siRNA techniques.

Retinal spheroids can be used i) for retinal tissue engineering, provided that appropriate stem cells become available, and ii) for developing living biosensors (e.g. testing of environmentally dangerous chemicals, such as pesticides), and thus can become valuable tools to reduce animal experimentation.

1948 born in Beutelsbach / Stuttgart, Germany.

1969 – 1973 Studies of food sciences in Stuttgart-Hohenheim.

1976 PhD at University of Konstanz under Prof. F. Hucho on Photoaffinty labeling of nicotinic cholinergic receptor and acetylcholinesterase.

1977 – 1979 Postdoc at Stanford School of Medicine, USA with Prof. E. Shooter. Signaltransduction & Degradation of Nerve growth factor (NGF).

1980 – 1991 Research on development of vertebrate brains and retina in department of Prof. A. Gierer at MPI for Devel. Biol., Tübingen; “Heisenberg”-grant. Habilitation in “Zoologie” at University of Tübingen.

1986, 1990 Extended research periods at the MPG-Guest laboratory at the Institute for Cell Biology, Academia Sinica, Shanghai, VR China.

since 1991 – 2015 Full Professor for Devel Biol & Neurogenetics at Technische Universität Darmstadt (TUDa). Teaching of Developmental, Human & Evolutionary Biology.

1995 – 1996 Director of the Institute for Zoology, TUDa.

1999 Invited Guest Professor for Cognitive & Brain Sciences, University of Tsukuba, Japan.

1993 – 1994 Dean of Faculty for Biology at TUDa (Fachbereich Biologie der TUDa)

2002 – 2005

1993-date Mentor for most qualified students from all disciplines at TUDa, supported by Studienstiftung des Deutschen Volkes. Award of Daidalos medal in 2013.

2015 retirement from teaching & research position.

2015-date Forschungsmentor of TUDa, supporting young investigators with their grant applications.

Manyfold international cooperations: EU, USA, China, India, Japan. Reviewer for international journals of neuroscience and developmental biology, as well as for many research foundations.

Publication of approx. 180 peer reviewed articles in internationally renowned journals on the following research topics: development of retina, brain vesicles, somites, trunk, appendages of chicken embryo and mouse embryos, establishment of retinal spheroid technologies, tissue engineering of retina, non-neuronal embryonic functions of cholinesterases and cholinergic systems, stem cell biology, radiation biology; science philosophy.

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