Selective control of neuronal cluster size at the forebrain/midbrain boundary by signaling from the prechordal plate

Abstract

Within the vertebrate embryonic neural plate, the first neuronal clusters often differentiate at the border of patterning identities. Whether the information inherent in the intersection of patterning identities alone controls all aspects of neuronal cluster development (location, identity, and size) is unknown. Here, we focus on the cluster of the medial longitudinal fascicle (nMLF) and posterior commissure (nPC), located at the forebrain/midbrain (fore/mid) boundary, to address this issue. We first identify expression of the transcription factor Six3 as a common and distinct molecular signature of nMLF and nPC neurons in zebrafish, and we use this marker to monitor mechanisms controlling the location and number of nMLF/nPC neurons. We demonstrate that six3 expression is induced at the fore/mid boundary in pax2.1/no-isthmus and smoothened/slow muscle omitted mutants, where identities adjacent to the six3 cluster are altered; however, in these mutants, the subpopulation of six3-positive cells located within the mispatterned territory is reduced. These results show that induction of the six3 cluster is triggered by the information derived from the intersection in patterning identities alone, whereas correct cluster size depends, in a modular manner, on the identities themselves. The size of the six3 cluster is also controlled independently of neural tube patterning: we demonstrate that the prechordal plate (PCP) is impaired in mixer/bonnie and clyde mutants and that this phenotype secondarily results in an increased production of six3-positive cells at the fore/mid boundary, without correlatively affecting patterning in this area. Thus, a signaling process originating from the PCP distinguishes between neural patterning and the control of six3 cluster size at the fore/mid junction in vivo. Together, our results suggest that a combination of patterning-related and -unrelated mechanisms specifically controls the size of individual early neuronal clusters within the anterior neural plate. Developmental Dynamics 227:524 -535, 2003.

Neurogenesis in zebrafish – from embryo to adult

“…These domains will be progressively recruited towards their neural fate during early neurogenesis. Members of the E(Spl) family, the Her/Hes genes, are transcriptional targets of SoxB1 , that is, her3 [58], and are expressed in various combinations in most domains of non-neurogenic territories, such as the other hairy genes her5 , her6 , her9 , and her11 [80,81]. Ectopic expression of these Her/Hes genes lead to a downregulation of neurog1 expression whereas loss-of-function experiments show an increase in neurog1 expression.…”

Transcriptional control of early tract formation in the embryonic chick midbrain

“…To unravel the molecular mechanisms that control the development of mlf and pc, we first studied the expression patterns of several homeobox genes around the ventral MFB. As a reference point for the subsequent expression studies, we employed Isl1 (Pfaff et al, 1996) to mark the oculomotor nucleus located just caudal and ventral to the INC. Sax1 (Schubert et al, 1995), Six3 (Bovolenta et al, 1998;Tallafuss et al, 2003), Emx2 (Agarwala and Ragsdale, 2002) and Pax6 (Sanders et al, 2002;Schubert et al, 1995) have all been previously described to be expressed in the ventral midbrain, dorsal to the oculomotor nucleus. However, their precise expression patterns with respect to each other and to specific early midbrain nuclei such as the INC have not been determined.…”

“…In addition, the repression of Emx2 and Six3 indicates an altered spatial patterning of the ventral MFB. In zebrafish, Six3 labels pc neurons as well as the INC (Tallafuss et al, 2003). Possibly, the specification of pc or mlf neurons depends on the balance of homeobox gene expression at the ventral MFB.…”

“…Very little is known about the molecular mechanisms that underlie the formation of the mlf and its contributing nucleus -the interstitial nucleus of Cajal (INC). Tight genetic regulation seems particularly important for distinguishing the fate of mlf neurons from those forming the posterior commissure (pc), as neurons for both tracts are located principally in the same ventral cluster at the midbrainforebrain border (MFB) (Tallafuss et al, 2003). Could homeobox genes play a role in specifying these early neuronal subtypes, and especially the mlf and pc cells?…”

Potenciais evocados auditivos de tronco encefálico na Holoprosencefali

“…Alguns autores sugerem a expressão do gene SIX3 na formação do tronco encefálico (Kikuta et al 2003, Tallafuss et al 2003.…”