Wnt5a gain- and loss-of-function present distinctly in craniofacial bone.

Area of Science:

• Developmental biology
• Genetics
• Craniofacial biology

Background:

• Robinow syndrome presents with craniofacial and dental anomalies.
• Gain- or loss-of-function variants in Wnt family member 5A (WNT5A) are implicated in Robinow syndrome.
• The precise role of Wnt5a in craniofacial and dental development remains unclear.

Purpose of the Study:

• To investigate the role of Wnt5a in craniofacial and dental development.
• To analyze the effects of Wnt5a loss-of-function (LOF) and gain-of-function (GOF) in bone cells.
• To correlate findings with Robinow syndrome phenotypes.

Main Methods:

• Utilized Wnt5a conditional LOF (Wnt5afl/fl;Ctskcre) and GOF (Rosa26-LSL-Wnt5a;Ctskcre) mouse models.
• Analyzed skulls from postnatal day 10 mice using micro-computed tomography and morphometrics.
• Assessed mandibular bone apoptosis via TUNEL staining.

Main Results:

• Wnt5a LOF led to midface hypoplasia, wider maxilla and basisphenoid, and delayed molar eruption.
• Wnt5a GOF resulted in macrocephaly, shortened palate, increased zygomatic length, and micrognathia.
• Both LOF and GOF exhibited partially penetrant snout deviation; GOF micrognathia was not due to apoptosis.

Conclusions:

• Craniofacial and dental phenotypes differed significantly between Wnt5a LOF and GOF, reflecting Robinow syndrome heterogeneity.
• Tooth eruption delay, mandibular condyle dysmorphology, and facial asymmetry were observed in altered Wnt5a mice.
• Precise regulation of Wnt5a is essential for proper craniofacial and dental development.