Fgfr1-dependent boundary cells between developing mid- and hindbrain

Abstract

Signaling molecules regulating development of the midbrain and anterior hindbrain are expressed in distinct bands of cells around the midbrain-hindbrain boundary. Very little is known about the mechanisms responsible for the coherence of this signaling center. One of the fibroblast growth factor (FGF) receptors, Fgfr1, is required for establishment of a straight border between developing mid- and hindbrain. Here we show that the cells close to the border have unique features. Unlike the cells further away, these cells express Fgfr1 but not the other FGF receptors. The cells next to the midbrain-hindbrain boundary express distinct cell cycle regulators and proliferate less rapidly than the surrounding cells. In Fgfr1 mutants, these cells fail to form a coherent band at the boundary. The slowly proliferating boundary cells are necessary for development of the characteristic isthmic constriction. They may also contribute to compartmentalization of this brain region.

Roles of jumonji and jumonji family genes in chromatin regulation and development

“…As described above, jmj negatively regulates proliferation of cardiac myocytes (Toyoda et al, 2003) and would repress the proliferation of neuroepithelial cells at the midbrain-hindbrain boundary (see above and Trokovic et al, 2005). Further evidence for a role for jmj in cell proliferation has been obtained in other cells as follows.…”

“…Of interest, a cyclin-dependent kinase inhibitor, p21Cip1 is also expressed at the same region as jmj. Expression of p21Cip1 and jmj decreased largely or disappeared while expression of cyclin D1 as well as cyclin D2 is enhanced in Fgfr1 KO embryos at E9.5-E10.5 (Trokovic et al, 2005). These results suggest that Fgfr1 signals enhance or maintain the expression of jmj and p21Cip1 and repress expression of cyclin D1 and D2 at a distinct region in the midbrainhindbrain boundary, resulting in slow proliferation at the region.…”

“…In fact, recent studies have shown that the cells in the boundary region proliferate less rapidly than the surrounding cells at E10.5 (Trokovic et al, 2005). Of interest, a cyclin-dependent kinase inhibitor, p21Cip1 is also expressed at the same region as jmj.…”

Analysis of the midbrain–hindbrain boundary cell fate using a boundary cell‐specific Cre‐mouse strain

“…In addition to the signaling function, several studies have given strong support for cell-lineage restriction and prevention of cell mixing across midbrain-hindbrain boundary (Langenberg and Brand, 2005;Millet et al, 1996;Zervas et al, 2004). The presence of boundaryspecific cell adhesion molecules (PB-cadherin, Kitajima et al, 1999;Trokovic, 2003) as well as cell cycle regulators (p21, Trokovic et al, 2005) implicates that a subpopulation of IsO cells closest to the midbrain-hindbrain boundary might have a unique identity. Here we report generation of transgenic mouse line expressing the Cre-recombinase in a boundary cell-specific fashion.…”

“…To define the population of recombinant cells in MHB-Cre/1; R26R/1 embryos, we compared b-gal expression pattern to the expression of Otx2, a marker of midbrain cells (Millet et al, 1996), as well as p21 and Cdh22 (PB-cadherin), markers of a recently identified boundary cell population (Trokovic et al, 2005). On adjacent sections of an E11.5 embryo, recombinant cells were located at both sides of the posterior border of the Otx2 expression domain (Fig.…”