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Front. Genet. | doi: 10.3389/fgene.2019.00977

Understanding the cellular and molecular mechanisms that control early cell fate decisions during appendicular skeletogenesis

  • 1National Autonomous University of Mexico, Mexico
  • 2National Institute of Rehabilitation, Mexico

The formation of the vertebrate skeleton is orchestrated in time and space by a number of gene regulatory networks that specify and position all skeletal tissues. During embryonic development, bones have two distinct origins: bone tissue differentiates directly from mesenchymal progenitors, whereas most long bones arise from cartilaginous templates through a process known as endochondral ossification. Before endochondral bone development takes place, chondrocytes decide between two fates, cartilage or joint, and thus activate either the cartilage differentiation programme or the joint formation programme. Once the cartilage differentiation programme starts, the growth plate begins to form. In contrast, when the joint formation programme is activated, a capsule begins to form that contains special articular cartilage and synovium to generate a functional joint.
In this review, we will discuss the mechanisms controlling the earliest molecular events that regulate cell fate during skeletogenesis in long bones. We will explore the initial processes that lead to the recruitment of mesenchymal stem/progenitor cells, the commitment of chondrocyte lineages and the formation of skeletal elements during morphogenesis. Thereafter, we will review the process of joint specification and joint morphogenesis. We will discuss the links between transcription factor activity, cell–cell interactions, cell–extracellular matrix interactions, growth factor signalling and other molecular interactions that control mesenchymal stem/progenitor cell fate during embryonic skeletogenesis.

Keywords: skeletal stem cells, Chondrogenesis, Endochondral bone development, Limb development, joint development, Cartilage differentiation

Received: 16 May 2019; Accepted: 13 Sep 2019.

Copyright: © 2019 Marin-Llera, Garciadiego-Cazares and Chimal-Monroy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Jessica C. Marin-Llera, National Autonomous University of Mexico, Mexico City, 04510, México, Mexico,
Dr. Jesus Chimal-Monroy, National Autonomous University of Mexico, Mexico City, 04510, México, Mexico,