Embryology Problem Based Question (Q2 - Langman)

ANATOMY AIIMS, GROSS ANATOMY, EMBRYOLOGY, NEUROANATOMY, MICROANATOMY, APPLIED/ CLINICAL ANATOMY

Under normal conditions, FGFs and their receptors (FGFRs) are responsible for growth of the skull and development of the cranial sutures. How might these signaling pathways be disrupted? Do these pathways involve paracrine or juxtacrine signaling? Can you think of a way that loss of expression of one FGF might be circumvented?

Answer:

Fibroblast Growth Factors (FGFs) are important signaling molecules that play a critical role in the development of the cranial sutures and the growth of the skull. These signaling pathways can be disrupted in various ways, such as mutations in the FGF genes, mutations in the FGFR genes, or alterations in the downstream signaling pathways that are involved in the regulation of FGF signaling.

The FGF signaling pathways involve both paracrine and juxtacrine signaling. In paracrine signaling, FGFs are secreted by one cell and act on neighboring cells that express FGFRs. In juxtacrine signaling, FGFs and FGFRs are expressed on adjacent cells and interact directly with each other. Both types of signaling are important for the proper development of the skull and cranial sutures.

Loss of expression of one FGF might be circumvented by compensatory upregulation of other FGFs. For example, in a study on Fgf9 knockout mice, compensatory upregulation of other FGFs was observed, leading to partial rescue of the phenotype. Additionally, exogenous application of FGFs might also be a way to circumvent the loss of expression of one FGF, although this would depend on the specific circumstances and would need to be tested experimentally.

References:

Rice DP, Aberg T, Chan YS, et al. Integration of FGF and TWIST in calvarial bone and suture development. Development. 2000;127(9):1845-1855. doi:10.1242/dev.127.9.1845

Wilkie AO. Craniosynostosis: genes and mechanisms. Hum Mol Genet. 1997;6(10):1647-1656. doi:10.1093/hmg/6.10.1647 Ohbayashi N, Shibayama M, Kurotaki Y, et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002;16(7):870-879. doi:10.1101/gad.976102