References: Hair growth and hair loss
Am J Pathol. 1997 Jan;150(1):209-22.
Type I (RI) and type II (RII) receptors for transforming growth factor-beta isoforms are expressed subsequent to transforming growth factor-beta ligands during excisional wound repair.
Gold LI, Sung JJ, Siebert JW, Longaker MT.
Department of Pathology, New York University Medical Center 10016, USA.
Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) regulate cell growth and differentiation and have critical regulatory roles in the process of tissue repair and remodeling. Signal transduction for TGF-beta function is transmitted by a heteromeric complex of receptors consisting of two serine/threonine kinase transmembrane proteins (RI and RII). We have previously shown that each TGF-beta isoform is widely expressed in a distinct spatial and temporal pattern throughout the processes of excisional and incisional wound repair. As the presence of TGF-beta receptors determines cellular responsiveness, we have currently examined, by immunohistochemistry, the localization of RI (ALK-1, ALK-5) and RII throughout repair of full-thickness excisional wounds up to 21 days after wounding. The expression of RI (ALK-5) and RII co-localized in both the unwounded and wounded skin and was present in the same cell types as TGF-beta ligands. However, immunoreactivity for TGF-beta receptors, throughout repair, occurred 1 to 5 days later than TGF-beta isoform immunostaining. This implies that the presence of TGF-beta ligands may up-regulate TGF-beta receptors for function and/or may reflect a lag due to local processing of latent TGF-beta. As observed for the immunohistochemical localization of TGF-beta isoforms in unwounded skin, RI and RII were expressed throughout the four layers of the epidermis, showing a wavy pattern of slight to moderate immunostaining, and hair follicles, sweat glands, and sebaceous glands were moderately immunoreactive. The extracellular matrix, fibroblasts, and blood vessels in the dermis were not immunoreactive. After injury, as observed for TGF-beta ligands, RI and RII expression was increased in the epidermis adjacent to the wound and the epithelium migrating over the wound was completely devoid of TGF-beta receptor immunoreactivity until re-epithelialization was completed by day 7 after wounding. The dermis was only slightly immunoreactive for RI and RII until day 5 when, immediately under the wound, immunostaining for fibroblasts, connective tissue cells, and newly forming vasculature began to increase and remained intense until day 14. Consistent with the role for TGF-beta in scarring, numerous fibroblasts, ostensibly active in the production of extracellular matrix components, continued to be slightly immunoreactive for RI and RII at 21 days. The ALK-1 (TSR-1) type I receptor, which binds both activin and TGF-beta, showed slight immunostaining early in repair (days 1 to 7) that progressively became more intense later in repair after day 10 and through day 21. This suggests that there may be a switch to a different type I receptor, implying different functions for the ALK-1 and ALK-5 receptors. The concomitant expression of TGF-beta isoforms and their signal-transducing receptors denote potential spatial and temporal activity of TGF-beta. Thus, although TGF-beta ligand is present, TGF-beta would not function in wound repair until a later time when RI and RII appear. This information should aid in the development of receptor antagonists as a therapeutic approach to scarring and fibrosis. In addition, these studies underscore the importance of defining the expression of proteins in vivo to establish a basis for the analysis of mechanisms in vitro.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9006337&dopt=Abstract
J Neurocytol. 1999 Oct-Nov;28(10-11):955-68.
A temporospatial map of adhesive molecules in the organ of Corti of the mouse cochlea.
Whitlon DS, Zhang X, Pecelunas K, Greiner MA.
Audiology and Hearing Sciences Program, Northwestern University, Evanston, IL, USA.
In the nervous system, several classes of cell-surface and extracellular matrix molecules have been implicated in processes such as neural growth, fasciculation, pathfinding, target recognition and synaptogenesis, which require cell-to-cell or cell-to-substrate binding. In the developing mouse cochlea, little is known about the types of cell-surface and extracellular matrix molecules existing along the neural growth paths or their possible roles in development. Whole mount and sectioned cochlear tissue were immunolabeled for six different adhesive molecules - neural cell adhesion molecule (NCAM), polysialic acid (PSA), neural cell adhesion molecule L1, E-cadherin, syndecan-1 and tenascin-C. A temporospatial map of adhesive molecule distribution in the basal turns of the mouse cochlea was generated. Distributions of adhesive molecules were compared to each other and to the known progress of neural development in the region. This comparison demonstrated differences in the complements of adhesive molecules between the inner and outer hair cell regions, and variations in the expressions of adhesion molecules among different types of nerve fibers. In addition, developmental changes in the adhesive environment around and beneath the outer hair cells coincided with the known timing of the appearance of morphologically defined efferent synapses. These observations raise the possibility that molecular differences at the cell surface of inner and outer hair cells are one way that ingrowing neurites distinguish different environments to determine their growth routes and synaptic partners in the cochlea. In addition these observations demonstrate the potential for differential signaling of afferent and efferent innervation by altering the microenvironments in which synapses are formed.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10900097&dopt=Abstract
biologie.uni-regensburg.de
The late prenatal and early postnatal development of the organ of Corti were studied in the horseshoe bat (Rhinolophus rouxi) by using scanning and transmission electron microscopy. Arrangements and dimensions of stereocilia bundles, together with their contacts with the tectorial membrane, were found to be adult-like shortly before birth, and thus before the biological onset of hearing (3-5 days after birth). During the first postnatal week, there were baso-apical gradients in disappearing kinocilia on inner hair cells (IHC), microvillis of supporting cells, and marginal pillars. The lower basal cochlear turn was mature with respect to these regressing structures at 3 days after birth, the apical turn at 10 days after birth. At birth, cytodifferentiation was found to be completed, and the tunnel of Corti and innermost spaces of Nuel had opened. The ultrastructure of IHCs was not markedly different from that at later ages. In outer hair cells (OHC), the adult-like regular arrangement of a single layer of subsurface cisternae and pillars was seen as soon as protrusions of supporting cells had withdrawn from the lateral wall of OHCs (basal turn at birth and throughout the cochlea 2 days after birth). Numerous efferent endings contacted the somata of IHCs up to the second postnatal week. Since the medial olivocochlear system is absent in horseshoe bats, the adult-like innervation pattern of OHCs was established at the biological onset of hearing. During the first 2 postnatal weeks, the cytoskeleton of pillar and Deiters cells, and the specialized Deiters cups developed. The organ of Corti appeared adult-like at 14 days, apart from the persistence of a reduced tympanic cover layer attached to the basilar membrane. Morphological data support physiological findings that the first broadly tuned auditory responses arise from the basal turn. The distinct low to high frequency gradient in development of sensitivity during the first 2 postnatal weeks of the horseshoe bat was not, however, matched by morphological gradients, and it would appear that the development of the cytoskeleton of supporting cells contributed to the establishment of tuning in the auditory fovea. Adult-like morphology of the organ of Corti coincided with the emergence of sharply tuned responses from the auditory fovea, but there was no clear-cut correlate for the shift in tuned foveal frequency representation that occurred during the following 3 weeks.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9007190&dopt=Abstract
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