Neural induction is one of the most important processes during vertebrate embryonic development, both because it is one of the earliest interactions between defined groups of cells in the normal embryo, and because this event initiates the development of the adult Central Nervous System (CNS). It was first described as an interaction between two groups of cells: the """"""""organizer"""""""" (which emits inducing signals) and the ectoderm (which responds to them by giving rise to the neural plate proper and to neural crest cells). Neural induction also initiates the regional subdivision of the CNS. Neural inducing signals are not confined to the organizer; the young neural plate itself can induce a neural plate from competent ectoderm (""""""""homeogenetic induction""""""""). Surprisingly, this phenomenon has not yet been studied in detail, and it is not even known whether homeogenetic induction is region-specific (for example: does forebrain induce forebrain?). Attempts to understand the molecular mechanisms of neural induction and regionalization in different species of vertebrates have produced contradictory results. However, the notion is starting to emerge that cooperation between several signaling pathways is involved in neural induction and the early patterning of the nervous system. In this project we will use a combination of molecular and embryological methods to investigate the earliest events leading to the induction and regionalization of the nervous system. Specifically, the aims are: A. To address the questions: Is the molecular mechanism of homeogenetic induction similar to induction by the organizer? Is homeogenetic induction region-specific? B. To characterize the regulation of 6 newly-identified genes that mark early responses of the ectoderm to grafts of the organizer (Hensen?s node) by different tissues and various secreted factors, and to begin to assess their functional roles in the neural induction process. C. To study the role of the novel Zinc finger gene Churchill in neural development by targeted inactivation in mouse. D. To explore the possible roles of 6 newly-identified candidate secreted factors in the early steps of neural induction and homeogenetic induction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060156-04
Application #
6641170
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Sieber, Beth-Anne
Project Start
1999-08-15
Project End
2006-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$162,000
Indirect Cost
Name
University College London
Department
Type
DUNS #
225410919
City
London
State
Country
United Kingdom
Zip Code
WC1 -6BT
De Almeida, Irene; Oliveira, Nidia M M; Randall, Rebecca A et al. (2017) Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction. Dev Biol 421:161-170
Papanayotou, Costis; De Almeida, Irene; Liao, Ping et al. (2013) Calfacilitin is a calcium channel modulator essential for initiation of neural plate development. Nat Commun 4:1837
Pinho, Sonia; Simonsson, Pamela R; Trevers, Katherine E et al. (2011) Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer. PLoS One 6:e19157
Gibson, Anna; Robinson, Neil; Streit, Andrea et al. (2011) Regulation of programmed cell death during neural induction in the chick embryo. Int J Dev Biol 55:33-43
Linker, Claudia; De Almeida, Irene; Papanayotou, Costis et al. (2009) Cell communication with the neural plate is required for induction of neural markers by BMP inhibition: evidence for homeogenetic induction and implications for Xenopus animal cap and chick explant assays. Dev Biol 327:478-86
de Almeida, Irene; Rolo, Ana; Batut, Julie et al. (2008) Unexpected activities of Smad7 in Xenopus mesodermal and neural induction. Mech Dev 125:421-31
Albazerchi, Amanda; Cinquin, Olivier; Stern, Claudio D (2007) A new method to transfect the hypoblast of the chick embryo reveals conservation of the regulation of an Otx2 enhancer between mouse and chick extraembryonic endoderm. BMC Dev Biol 7:25
Linker, Claudia; Stern, Claudio D (2004) Neural induction requires BMP inhibition only as a late step, and involves signals other than FGF and Wnt antagonists. Development 131:5671-81
Sheng, Guojun; dos Reis, Mario; Stern, Claudio D (2003) Churchill, a zinc finger transcriptional activator, regulates the transition between gastrulation and neurulation. Cell 115:603-13
Skromne, Isaac; Stern, Claudio D (2002) A hierarchy of gene expression accompanying induction of the primitive streak by Vg1 in the chick embryo. Mech Dev 114:115-8

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