Molecular mechanisms controlling brain development: an overview of neuroepithelial secondary organizers

Abstract

. In this review, we will describe the principle aspects of CNS development in birds and mammals, starting from early stages of embryogenesis (gastrulation and neurulation) and culminating with the formation of a variety of different regions which contribute to the structural complexity of the brain (regionalization and morphogenesis). We will pay special attention to the cellular and molecular mechanisms involved in neural tube regionalization and the key role played by localized secondary organizers in the patterning of neural primordia. KEY WORDS: patterning, neural plate, neural tube, gastrulation, neurulation, secondary organizer, anterior neural ridge, zona limitans intrathalamica, isthmic organizer Neural plate and neural tube formationA fundamental early step in neural development is the allocation of a group of ectodermal cells as precursors of the entire nervous system (Hemmati-Brivanlou and Melton, 1997). This process involves an inductive interaction first demonstrated in amphibian embryos by Spemann and Mangold in the 1920's (see Spemann and Mangold, 2001). Their experiments which involved the grafting of differently pigmented species of newt established the concept of neural induction as an instructive interaction between the dorsal lip of the blastopore (the "organizer") and the neighboring ectoderm. The discovery of a neural organization center for the amphibian gastrula initiated a search for homologous structures in other vertebrates. Soon thereafter, the equivalent region was discovered in most vertebrate species, including the shield of teleosts. In birds and mammals, the region was named "Hensen's node" and "the node", respectively. When C.H. Waddington transplanted the Hensen node of a chick embryo, he observed the induction of Int. J. Dev. Biol. 54: 7-20 (2010) Abbreviations used in this paper: ANR, anterior neural ridge; AP, anteroposterior; BMP, bone morphogenetic protein; DV, dorso-ventral; FGF, fibroblast growth factor; IsO, Isthmic organizer; ML, medio-lateral; TGF, transforming growth factor; ZLI, zona limitans intrathalamica.an ectopic neural plate or the formation of a partial new embryonic axis containing neural tube, notochord and somites (Waddington, 1933;Waddington, 1936). This demonstration provided the first evidence that in chick embryos, the nervous system is induced by signals from non-neural cells. Recent works demonstrated that the capacity of ectodermal cells to undergo neural differentiation represents their default state. In fact, neural differentiation must be suppressed in the lateral ectoderm by signals transmitted between neighboring cells, in order to develop as epidermis. These molecular signals are members of the bone morphogenetic protein (BMP) subclass of transforming growth factor β (TGF-β)-related proteins (for review see Wittler and Kessel, 2004). C. Vieira et al.Recent studies using chick embryos have shown that neural induction really begins prior to the formation of the organizer region and thus must be initiated by signals derived from other cellul...

Wnt Signal Specifies the Intrathalamic Limit and Its Organizer Properties by Regulating Shh Induction in the Alar Plate

“…In the diencephalon, Shh is the main signal expressed in the ZLI, a transverse morphogenetic organizer controlling anteroposterior diencephalic regionalization and thalamic nuclear organization in vertebrates (Echevarría et al, 2003;Vieira et al, 2005Vieira et al, , 2010 for review, see Scholpp and Lumsden, 2010).…”

Clonal and molecular analysis of the prospective anterior neural boundary in the mouse embryo

“…The definition of the ANR varies between vertebrate models, resulting in some inconsistencies in fate maps obtained by grafting or DiIlabelling methods. Fgf8 expression is often used to define the location of the ANR (Shimamura and Rubenstein, 1997;Vieira et al, 2010), but the onset and extent of Fgf8 expression vary depending on the species and the developmental stage considered. Here, we define the ANR, on the basis of Fgf8 expression, as the region encompassing the rostralmost part of the forebrain neuroectodem and the underlying VEAP at the 5-to 7-somite stage.…”

“…FGF signalling in the anterior neural ridge (ANR), at the junction between anterior neural and non-neural ectoderm, regulates forebrain development and patterning (Shimamura and Rubenstein, 1997;Shanmugalingam et al, 2000;Paek et al, 2009). Various anterior defects, including absence or reduction of the telencephalic vesicles, eyes, olfactory placodes and frontonasal structures, and truncation of the structures rostral to the zona limitans intrathalamica (ZLI), have been consistently associated with a reduction of Fgf8 expression in the ANR (Dattani et al, 1998;Meyers et al, 1998;Acampora et al, 2000;Crossley et al, 2001;Kobayashi et al, 2002;Suda et al, 2001;Tian et al, 2002;Zoltewicz et al, 2009;Vieira et al, 2010).…”

The facial neural crest controls fore- and midbrain patterning by regulating Foxg1 expression through Smad1 activity

“…Deficits can be overcome by supplying an exogenous source of Fgf8 (Shimamura and Rubenstein, 1997). Other brain-organising centres secreting Wnt and Shh molecules along the dorsal and ventral midlines are also required for brain development (McMahon and Bradley, 1990;Kim et al, 2001;Chang et al, 2004;Danesin et al, 2009;Vieira et al, 2010). Collectively, these factors generate a matrix of combinatorial morphogenetic factors, which governs planar specification and imparts a certain degree of molecular regionalisation to the cerebral neuroepithelium (Echevarría et al, 2003;Hoch et al, 2009).…”