Little is known about the genesis and patterning of tendons and other connective tissues, mostly owing to the absence of early markers We have found that Scleraxis, a bHLH transcription factor, is a highly specific marker for all the connective tissues that mediate attachment of muscle to bone in chick and mouse, including the limb tendons, and show that early scleraxis expression marks the progenitor cell populations for these tissues In the early limb bud, the tendon progenitor population is found in the superficial proximomedial mesenchyme Using the scleraxis gene as a marker we show that these progenitors are induced by ectodermal signals and restricted by bone morphogenetic protein (BMP) signaling within the mesenchyme Application of Noggin protein antagonizes this endogenous BMP activity and induces ectopic scleraxis expression However, the presence of excess tendon progenitors does not lead to the production of additional or longer tendons, indicating that additional signals are required for the final formation of a tendon Finally, we show that the endogenous expression of noggin within the condensing digit cartilage contributes to the induction of distal tendons

Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments

https://www.oarsijournal.com/article/S1063-4584(99)90306-0/pdf

Cellular interactions and signaling in cartilage development.

Little is known about the regulatory signals involved in tendon and ligament formation, and this lack of understanding has hindered attempts to develop biologically based therapies for tendon and ligament repair. Here we report that growth and differentiation factors (GDFs) 5, 6, and 7, members of the TGF-beta gene superfamily that are most related to the bone morphogenetic proteins, induce neotendon/ligament formation when implanted at ectopic sites in vivo. Analysis of tissue induced by GDF-5, 6, or 7, containing implants by currently available morphological and molecular criteria used to characterize tendon and ligament, adds further evidence to the idea that these GDFs act as signaling molecules during embryonic tendon/ligament formation. In addition, comparative in situ localizations of the GDF-5, 6, and 7 mRNAs suggest that these molecules are important regulatory components of synovial joint morphogenesis.

/pdf/ectopic-induction-of-tendon-and-ligament-in-rats-by-growth-33j9ng8ddl.pdf

Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family.

A Somitic Compartment of Tendon Progenitors

The proper development of the musculoskeletal system in the tetrapod limb requires the coordinated development of muscle, tendon and cartilage. This paper examines the morphogenesis of muscle and tendon in the developing avian hind limb. Based on a developmental series of embryos labeled with myosin and tenascin antibodies in whole mount, an integrative description of the temporal sequence and spatial pattern of muscle and tendon morphogenesis and their relationship to cartilage throughout the chick hind limb is presented for the first time. Anatomically distinct muscles arise by the progressive segregation of muscle: differentiated myotubes first appear as a pair of dorsal and ventral muscle masses; these masses subdivide into dorsal and ventral thigh, shank and foot muscle masses; and finally these six masses segregate into individual muscles. From their initial appearance, most myotubes are precisely oriented and their pattern presages the pattern of future, individual muscles. Anatomically distinct tendons emerge from three tendon primordia associated with the major joints of the limb. Contrary to previous reports, comparison of muscle and tendon reveals that much of their morphogenesis is temporally and spatially closely associated. To test whether reciprocal muscle-tendon interactions are necessary for correct muscle-tendon patterning or whether morphogenesis of each of these tissues is autonomous, two sets of experiments were conducted: (1) tendon development was examined in muscleless limbs produced by coelomic grafting of early limb buds and (2) muscle development was analyzed in limbs where tendon had been surgically altered. These experiments demonstrate that in the avian hind limb the initial morphogenetic events, formation of tendon primordia and initial differentiation of myogenic precursors, occur autonomously with respect to one another. However, later morphogenetic events, such as subdivision of muscle masses and segregation of tendon primordia into individual tendons, do require to various degrees reciprocal interactions between muscle and tendon. The dependence of these later morphogenetic events on tissue interactions differs between different proximodistal regions of the limb.

Muscle and tendon morphogenesis in the avian hind limb

Experimental analysis of the role of ECM in the patterning of the distal tendons of the developing limb bud

The extracellular matrix architecture relating to myotendinous pattern formation in the distal part of the developing chick limb: An ultrastructural, histochemical and immunocytochemical analysis

During later developmental stages (27–36 HH) the formation of the long autopodial tendons of the chick leg seems to be governed by a precise pattern of extracellular material (ECM). The main element of this pattern is a tenascin-rich sheet termed the “mesenchyme lamina” (ML) which originates at the basement membrane distally and runs proximally through the mesoderm, subjacent and parallel to the basement membrane (Hurle et al, 1989),Immunohistochemistry showed that the lamina strongly reacted to tenascin and collagen type I but weakly to fibronectin and failed to react to laminin and collagen type IV, clearly differentiating it from the basement membrane.

M. A. Critchlow

Papers

Experimental analysis of the role of ECM in the patterning of the distal tendons of the developing limb bud

The extracellular matrix architecture relating to myotendinous pattern formation in the distal part of the developing chick limb: An ultrastructural, histochemical and immunocytochemical analysis

Extracellular Material Organization and Long Tendon Formation in the Chick Leg Autopodium. In Vivo and in Vitro Study