title: The tumor suppressor BTG1 is expressed in the developing digits and regulates skeletogenic differentiation of limb mesodermal progenitors in high density cultures.
abstract: In the developing limb, differentiation of skeletal progenitors towards distinct connective tissues of the digits is correlated with the establishment of well-defined domains of Btg1 gene expression. Zones of high expression of Btg1 include the earliest digit blastemas, the condensing mesoderm at the tip of the growing digits, the peritendinous mesenchyme, and the chondrocytes around the developing interphalangeal joints. Gain- and loss-of function experiments in micromass cultures of skeletal progenitors reveal a negative influence of Btg1 in cartilage differentiation accompanied by up-regulation of Ccn1, Scleraxis and PTHrP. Previous studies have assigned a role to these factors in the aggregation of progenitors in the digit tips (Ccn1), in the differentiation of tendon blastemas (Scleraxis) and repressing hypertrophic cartilage differentiation (PTHrP). Overexpression of Btg1 up-regulates the expression of retinoic acid and thyroid hormone receptors, but, different from other systems, the influence of BTG1 in connective tissue differentiation appears to be independent of retinoic acid and thyroid hormone signaling.
authors.affiliation: Departamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, Santander, 39011, Spain.
authors.forename: Carlos I
authors.initials: CI
authors.lastname: Lorda-Diez
authors.affiliation: Departamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, Santander, 39011, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Montero
authors.affiliation: Departamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, Santander, 39011, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Garcia-Porrero
authors.affiliation: Departamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, Santander, 39011, Spain. hurlej@unican.es.
authors.forename: Juan M
authors.identifier: 0000-0002-4685-025X
authors.initials: JM
authors.lastname: Hurle
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D002356:Cartilage / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology*; D055515:Cysteine-Rich Protein 61 / Q000096:biosynthesis; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology; D014034:Toes / Q000196:embryology*; D014212:Tretinoin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055515:Cysteine-Rich Protein 61; D009363:Neoplasm Proteins; D044162:Parathyroid Hormone-Related Protein; D011988:Receptors, Thyroid Hormone; D014212:Tretinoin; C489552:Btg1 protein, mouse; C491850:CCN1 protein, mouse; C503815:Scx protein, mouse
keywords: Cartilage hypertrophy; Ccn1; Limb development; PTHrP; Prechondrogenic aggregates