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

Abstract

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 Fgf10. Fgf10+ 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 gives 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.

Sonic hedgehog in vertebrate neural tube development

“…Studies in chick and mouse show that RDVM cells give rise to a highly proliferative hypothalamic progenitor population (Manning et al, 2006;Alvarez-Bolado et al, 2012;Fu et al, 2017). The transition from RDVM to proliferating hypothalamic progenitors appears to be mediated by the PM.…”

“…Recent fate-mapping experiments in chick and mouse show that RDVM-derived hypothalamic progenitors are a multipotent population and contribute widely to different subsets of hypothalamic progenitors (Alvarez-Bolado et al, 2012;Fu et al, 2017). In chick, RDVM-derived hypothalamic progenitors give rise to anterior, tuberal and mamillary progenitors along the rostro-caudal axis,, each of which grows and differentiates sequentially over time (Fu et al, 2017).…”

“…In chick, RDVM-derived hypothalamic progenitors give rise to anterior, tuberal and mamillary progenitors along the rostro-caudal axis,, each of which grows and differentiates sequentially over time (Fu et al, 2017). This shows an exquisite coupling of growth and fate in the hypothalamus, a process in which Shh signaling plays an essential role.…”

“…This shows an exquisite coupling of growth and fate in the hypothalamus, a process in which Shh signaling plays an essential role. Transient blockade of Shh signaling in the chick embryo prevents the growth of anterior progenitors (Fu et al, 2017). Studies in mouse and zebrafish suggests a potential mechanism, in which Shh induces the paired-like homeodomain TF, Rx/rx3 in hypothalamic progenitors, a determinant of anterior progenitor fate and growth.…”

Development of the basal hypothalamus through anisotropic growth

“…Recent work in the embryonic chick, which examines the growth of a previously‐undefined progenitor population, now suggests that progenitor displacement/migration is key to hypothalamic development, and suggests a fundamentally different model of hypothalamic development to those previously suggested. Here, we summarise these studies and describe an “anisotropic growth model” of hypothalamic development.…”