Temporal requirement of Hoxa2 in cranial neural crest skeletal morphogenesis.
Little is known about the spatiotemporal requirement of Hox gene patterning activity in vertebrates. In Hoxa2 mouse mutants, the hyoid skeleton is replaced by a duplicated set of mandibular and middle ear structures. Here, we show that Hoxa2 is selectively required in cranial neural crest cells (NCCs). Moreover, we used a Cre-ERT2 recombinase system to induce a temporally controlled Hoxa2 deletion in the mouse. Hoxa2 inactivation after cranial NCC migration into branchial arches resulted in homeotic transformation of hyoid into mandibular arch skeletal derivatives, reproducing the conventional Hoxa2 knockout phenotype, and induced rapid changes in Alx4, Bapx1, Six2 and Msx1 expression patterns. Thus, hyoid NCCs retain a remarkable degree of plasticity even after their migration in the arch, and require Hoxa2 as an integral component of their morphogenetic program. Moreover, subpopulations of postmigratory NCCs required Hoxa2 at discrete time points to pattern distinct derivatives. This study provides the first temporal inactivation of a vertebrate Hox gene and illustrates Hox requirement during late morphogenetic processes.
Santagati
Fabio
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, UMR 7104, BP 10142, CU de Strasbourg, 67404 Illkirch Cedex, France.
Minoux
Maryline
M
Ren
Shu-Yue
SY
Rijli
Filippo M
FM
D000818:Animals; D001934:Branchial Region / Q000196:embryology; D004431:Ear, External / Q000002:abnormalities / Q000196:embryology; D004432:Ear, Middle / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology*; D012886:Skull / Q000196:embryology*; D013997:Time Factors
D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse