TY - JOUR
T1 - Ofd1 is required in limb bud patterning and endochondral bone development
AU - Bimonte, Sabrina
AU - De Angelis, Amalia
AU - Quagliata, Luca
AU - Giusti, Fabiola
AU - Tammaro, Roberta
AU - Dallai, Romano
AU - Ascenzi, Maria Grazia
AU - Diez-Roux, Graciana
AU - Franco, Brunella
PY - 2011/1/15
Y1 - 2011/1/15
N2 - Oral-facial-digital type I (OFDI) syndrome is an X-linked male lethal developmental disorder. It is ascribed to ciliary dysfunction and characterized by malformation of the face, oral cavity, and digits. Conditional inactivation using different Cre lines allowed us to study the role of the Ofd1 transcript in limb development. Immunofluorescence and ultrastructural studies showed that Ofd1 is necessary for correct ciliogenesis in the limb bud but not for cilia outgrowth, in contrast to what was previously shown for the embryonic node. Mutants with mesenchymal Ofd1 inactivation display severe polydactyly with loss of antero-posterior (A/P) digit patterning and shortened long bones. Loss of digit identity was found to be associated with a progressive loss of Shh signaling and an impaired processing of Gli3, whereas defects in limb outgrowth were due to defective Ihh signaling and to mineralization defects during endochondral bone formation.Our data demonstrate that Ofd1 plays a role in regulating digit number and identity during limb and skeletal patterning increasing insight on the functional role of primary cilia during development.
AB - Oral-facial-digital type I (OFDI) syndrome is an X-linked male lethal developmental disorder. It is ascribed to ciliary dysfunction and characterized by malformation of the face, oral cavity, and digits. Conditional inactivation using different Cre lines allowed us to study the role of the Ofd1 transcript in limb development. Immunofluorescence and ultrastructural studies showed that Ofd1 is necessary for correct ciliogenesis in the limb bud but not for cilia outgrowth, in contrast to what was previously shown for the embryonic node. Mutants with mesenchymal Ofd1 inactivation display severe polydactyly with loss of antero-posterior (A/P) digit patterning and shortened long bones. Loss of digit identity was found to be associated with a progressive loss of Shh signaling and an impaired processing of Gli3, whereas defects in limb outgrowth were due to defective Ihh signaling and to mineralization defects during endochondral bone formation.Our data demonstrate that Ofd1 plays a role in regulating digit number and identity during limb and skeletal patterning increasing insight on the functional role of primary cilia during development.
KW - Endochondral bone development
KW - Limb and skeletal patterning
KW - Limb development
KW - OFD1
KW - Primary cilia
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U2 - 10.1016/j.ydbio.2010.09.020
DO - 10.1016/j.ydbio.2010.09.020
M3 - Article
C2 - 20920500
AN - SCOPUS:78650843442
VL - 349
SP - 179
EP - 191
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -