Building a bridal chamber: development of the thalamus

Abstract

The thalamus is a central brain region that plays a crucial role in distributing incoming sensory information to appropriate regions of the cortex. The thalamus develops in the posterior part of the embryonic forebrain, where early cell fate decisions are controlled by a local signaling center - the mid-diencephalic organizer - which forms at the boundary between prospective prethalamus and thalamus. In this review we discuss recent observations of early thalamic development in zebrafish, chick, and mouse embryos, that reveal a conserved set of interactions between homeodomain transcription factors. These interactions position the organizer along the neuraxis. The most prominent of the organizer's signals, Sonic hedgehog, is necessary for conferring regional identity on the prethalamus and thalamus and for patterning their differentiation.

Figure 1

Development of the mid-diencephalic organizer. (a) The MDO is induced at the interface of the Fez-positive prethalamus anlage and the Otx-positive MDO/thalamus anlage. (b) Following induction, the principal signal of the MDO – Shh – is expressed from ventral to dorsal, possibly limited dorsally by RA signaling from the epithalamus. (c) Shh expression within the MDO is limited anteroposteriorly by the repressive function of neighboring transcription factors, Fez and Irx. Expression of Fez and Irx establish the prethalamic and thalamic anlagen as differentially competent fields, determining their subsequent response to Shh signaling from the MDO. Ep, epithalamus; MDO,mid-diencephalic organizer; M/T, anlage of the mid-diencephalic organizer and thalamus; P, prethalamic anlage.

Figure 2

Three steps in regionalization of the thalamus. (a) The transcription factors Fez and Irx define properties anteriorly and posteriorly to the MDO. (b) The bHLH factor Her6 determines neuronal identity: in the Her6-positive domains, Shh induces Ascl1, and in the Her6-negative domain, Shh induces Neurogenin1 (Neurog1). (c) Shh (red) influences the sizes of the thalamic nuclei by a Shh protein concentration gradient (fading red). cT, caudal thalamus; PTh, prethalamus; rT, rostral thalamus; Th, thalamus.

Figure 3

Comparative expression of thalamic markers in mouse, chick and zebrafish during embryonic development. Colored bars show the expression dynamics of genes expressed within the thalamic territory. Same colors indicate homologs or members of one gene family (such as FezF1 and FezF2). Expression dynamics in different model organisms have been staged according to two time points: induction of Shh in the MDO and its patterning activity from the mature MDO. Otx2, Fez, and Irx are involved in induction and positioning of the MDO, and Shh is the principal signaling molecule in the MDO. The prethalamic genes, Ascl1 and Dlx2, and the thalamic genes, neurogenin (neurog1 and 2) and gbx2, are target genes of Shh signaling. Fez expression has not yet been documented in chick. References to the relevant literature are given at the right hand site in square brackets.

Figure 4

Evolution of the MDO. Expression of Shh (red) with the flanking expression domain of Nkx2.2 (blue), the prethalamic marker FezF (yellow) and the thalamic marker Otx (green) in the thalamic complex in agnathans (lamprey) and gnathostomes (zebrafish, mouse). Note that Shh is not expressed in the anterior neural tissue in Amphioxus (a cephalochordate) but in the underlying tip of the notochord (No). Data on Fez expression in lamprey are missing (grey). In Saccoglossus (a hemichordate) Shh is expressed in a narrow strip that lies between the Fez and Otx domain, just as in vertebrates, suggesting a basal chordate origin for the MDO. Expression summary in Amphioxus and lamprey is based on different, non-comparative publications. Except for Shh, expression domains are shown only for the thalamic complex. Hb, hindbrain; Hy, hypothalamus; Mb, midbrain; No, notochord; Pa, pallium, SPa, subpallium; Tel, telencephalon.