Parrillo, Luca
(2009)
Gene expression profiles during thyroid embryonic development.
[Tesi di dottorato]
(Inedito)
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Gene expression profiles during thyroid embryonic development |
| Autori: |
| Autore | Email |
|---|
| Parrillo, Luca | lparrillo@alice.it |
|
| Data: |
30 Novembre 2009 |
| Numero di pagine: |
77 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Biologia e patologia cellullare e molecolare "L. Califano" |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Genetica e medicina molecolare |
| Ciclo di dottorato: |
22 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Di Lauro, Roberto | dilauro@szn.it |
|
| Tutor: |
| nome | email |
|---|
| Di Lauro, Roberto | dilauro@szn.it |
|
| Data: |
30 Novembre 2009 |
| Numero di pagine: |
77 |
| Parole chiave: |
congenital hypothyroidism, laser capture microdissection, microarrays |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 05 - Scienze biologiche > BIO/18 - Genetica |
[error in script]
[error in script]
| Depositato il: |
19 Mag 2010 12:51 |
| Ultima modifica: |
30 Apr 2014 19:38 |
| URI: |
http://www.fedoa.unina.it/id/eprint/3817 |
| DOI: |
10.6092/UNINA/FEDOA/3817 |
Abstract
Congenital Hypothyroidism (CH) is commonly due to structural defects of thyroid gland, collectively known as thyroid dysgenesis. Defects in growth and/or differentiation of the thyroid primordium can result in an absent (athyreosis) or hypoplastic thyroid; an impaired migration of thyroid precursor cells causes an ectopic gland (Van Vliet G, 2003). The clinical picture of thyroid dysgenesis thus suggests that defects of the specification, survival and movement of thyroid precursor cells are the key aberrations in CH. Understanding the regulation of early thyroid morphogenesis is thus important to elucidate the pathogenesis of CH. Murine models with target inactivation of the transcription factors Nkx2.1, Pax8, Foxe1 and Hhex expressed in thyroid progenitor cells and in the adult gland have demonstrated their important functions in thyroid development (De Felice M and Di Lauro R, 2004). Even though the thyroid is specified in each of these models it later disappears suggesting a role of these transcription factors also in the survival and expansion of the thyroid progenitors cell population. However, very few germ-line mutations have been detected in the corresponding genes of human patients with thyroid dysgenesis (Al Taji et al., 2007) suggesting the importance of additional genes. The aim of this thesis has been to discovery these genes by an unbiased search for transcripts enriched in the early thyroid primordium. Mouse thyroid primordia at the bud stage (E10.5) were isolated by laser capture microdissection (LCM). In parallel, RNA from whole embryos was obtained. RNA was amplified and labelled; samples were hybridized to Affymetrix microarrays. Bioinformatic analysis tools identified over 3000 transcripts as significantly enriched in the thyroid bud as compared to expression in the whole embryo. Such an enrichment is expressed as Fold Change (FC), 450 transcripts out 3000 displayed a FC >5. High and restricted expression of several of these in the E10.5 thyroid bud was confirmed experimentally by in situ hybridization on mouse embryos. This preliminary analysis indicates that the list has a high degree of validity. By this approach I have identified a large number of transcripts enriched in the embryonic thyroid bud with currently unknown functions in its development. This list will be an important resource in further efforts to elucidate the genetic networks that govern thyroid morphogenesis and might underlie CH.
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