Fgf10(+) progenitors give rise to the chick hypothalamus by rostral and caudal growth and differentiation

Classical descriptions of the hypothalamus divide it into three rostro-caudal domains but little is known about their embryonic origins. To investigate this we performed targeted fate-mapping, molecular characterisation and cell cycle analyses in the embryonic chick. Presumptive hypothalamic cells derive from the rostral diencephalic ventral midline, lie above the prechordal mesendoderm and express Fgf10Fgf10(+) progenitors undergo anisotropic growth: those displaced rostrally differentiate into anterior cells, then those displaced caudally differentiate into mammillary cells. A stable population of Fgf10(+) progenitors is retained within the tuberal domain, a subset of these give rise to the tuberal infundibulum, the precursor of the posterior pituitary. Pharmacological approaches reveal that Shh signalling promotes the growth and differentiation of anterior progenitors and also orchestrates the development of the infundibulum and Rathke's pouch, the precursor of the anterior pituitary. Together our studies identify a hypothalamic progenitor population defined by Fgf10 and highlight a role for Shh signalling in the integrated development of the hypothalamus and pituitary

Ontogenetic Expression of Sonic Hedgehog in the Chicken Subpallium

Sonic hedgehog (SHH) is a secreted signaling factor that is implicated in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates. SHH has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. It is secreted early in development by the axial mesoderm (prechordal plate and notochord) and the overlying ventral neural tube. Recent studies clarified the impact of SHH signaling mechanisms on dorsoventral patterning of the spinal cord, but the corresponding phenomena in the rostral forebrain are slightly different and more complex. This notably involves separate Shh expression in the preoptic part of the forebrain alar plate, as well as in the hypothalamic floor and basal plates. The present work includes a detailed spatiotemporal description of the singular alar Shh expression pattern in the rostral preoptic forebrain of chick embryos, comparing it with FoxG1, Dlx5, Nkx2.1, and Nkx2.2 mRNA expression at diverse stages of development. As a result of this mapping, we report a subdivision of the preoptic region in dorsal and ventral zones; only the dorsal part shows Shh expression. The positive area impinges as well upon a median septocommissural preoptic domain. Our study strongly suggests tangential migration of Shh-positive cells from the preoptic region into other subpallial domains, particularly into the pallidal mantle and the intermediate septum

Opposing Shh and Fgf signals initiate nasotemporal patterning of the zebrafish retina.

The earliest known determinants of retinal nasotemporal identity are the transcriptional regulators Foxg1, which is expressed in the prospective nasal optic vesicle, and Foxd1, which is expressed in the prospective temporal optic vesicle. Previous work has shown that, in zebrafish, Fgf signals from the dorsal forebrain and olfactory primordia are required to specify nasal identity in the dorsal, prospective nasal, optic vesicle. Here, we show that Hh signalling from the ventral forebrain is required for specification of temporal identity in the ventral optic vesicle and is sufficient to induce temporal character when activated in the prospective nasal retina. Consequently, the evaginating optic vesicles become partitioned into prospective nasal and temporal domains by the opposing actions of Fgfs and Shh emanating from dorsal and ventral domains of the forebrain primordium. In absence of Fgf activity, foxd1 expression is established irrespective of levels of Hh signalling, indicating that the role of Shh in promoting foxd1 expression is only required in the presence of Fgf activity. Once the spatially complementary expression of foxd1 and foxg1 is established, the boundary between expression domains is maintained by mutual repression between Foxd1 and Foxg1

Adhesive/Repulsive Codes in Vertebrate Forebrain Morphogenesis.

The last fifteen years have seen the identification of some of the mechanisms involved in anterior neural plate specification, patterning, and morphogenesis, which constitute the first stages in the formation of the forebrain. These studies have provided us with a glimpse into the molecular mechanisms that drive the development of an embryonic structure, and have resulted in the realization that cell segregation in the anterior neural plate is essential for the accurate progression of forebrain morphogenesis. This review summarizes the latest advances in our understanding of mechanisms of cell segregation during forebrain development, with and emphasis on the impact of this process on the morphogenesis of one of the anterior neural plate derivatives, the eyes

LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease

To fulfill their multiple roles in organ development and adult tissue homeostasis Hedgehog morphogens (HH) act through their receptor Patched (PTCH) on target cells. However, HH actions also require HH binding proteins, auxiliary cell surface receptors that agonize or antagonize morphogen signaling in a context-dependent manner. Here, we discuss recent findings on the LDL receptor-related protein 2 (LRP2), an exemplary HH binding protein that modulates sonic hedgehog activities in stem and progenitor cell niches in embryonic and adult tissues. LRP2 functions are crucial for developmental processes in a number of tissues, including the brain, the eye, and the heart, and defects in this receptor pathway are the cause of devastating congenital diseases in humans

Ontogenetic expression of sonic hedgehog in the chicken subpallium

International audienceSonic hedgehog (SHH) is a secreted signaling factor that is implicated in the molecular patterning of the central nervous system (CNS), somites, and limbs in vertebrates. SHH has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. It is secreted early in development by the axial mesoderm (prechordal plate and notochord) and the overlying ventral neural tube. Recent studies clarified the impact of SHH signaling mechanisms on dorsoventral patterning of the spinal cord, but the corresponding phenomena in the rostral forebrain are slightly different and more complex. This notably involves separate Shh expression in the preoptic part of the forebrain alar plate, as well as in the hypothalamic floor and basal plates. The present work includes a detailed spatiotemporal description of the singular alar Shh expression pattern in the rostral preoptic forebrain of chick embryos, comparing it with FoxG1, Dlx5, Nkx2.1, and Nkx2.2 mRNA expression at diverse stages of development. As a result of this mapping, we report a subdivision of the preoptic region in dorsal and ventral zones; only the dorsal part shows Shh expression. The positive area impinges as well upon a median septocommissural preoptic domain. Our study strongly suggests tangential migration of Shh-positive cells from the preoptic region into other subpallial domains, particularly into the pallidal mantle and the intermediate septum

Adenohypophysis placodal precursors exhibit distinctive features within the rostral preplacodal ectoderm

Placodes are discrete thickenings of the vertebrate cranial ectoderm that generate morpho-functionally distinct structures, such as the adenohypophysis, olfactory epithelium and lens. All placodes arise from a horseshoe-shaped preplacodal ectoderm in which the precursors of individual placodes are intermingled. However, fate-map studies indicated that cells positioned at the preplacodal midline give rise to only the adenohypophyseal placode, suggesting a unique organization of these precursors within the preplacode. To test this possibility, we combined embryological and molecular approaches in chick embryos to show that, at gastrula stage, adenohypophyseal precursors are clustered in the median preplacodal ectoderm, largely segregated from those of the adjacent olfactory placode. Median precursors are elongated, densely packed and, at neurula stage, express a molecular signature that distinguishes them from the remaining preplacodal cells. Olfactory placode precursors and midline neural cells can replace ablated adenohypophyseal precursors up to head-fold stage, although with a more plastic organization. We thus propose that adenohypophyseal placode precursors are unique within the preplacodal ectoderm possibly because they originate the only single placode and the only one with an endocrine character.</jats:p