Transcription gene mutations proven to be associated with thyroid dysgenesis are PAX8, TTF-2, NKX2.1
, and NXK2.5.3 The clinical findings observed on these mutations are summarized in (Table-2).
Lung atelectasis in mutants correlated with reduced levels of NKX2.1
(TITF1; 600635) and surfactant (SFTPA1; 178630).
In addition, mutations in genes FOXE1, PAX8, TSHR, NKX2.1
, or NKX2.5 associated with TD were identified in only 2-3% of TD cases .
Simultaneously, several studies have shown that thyroid transcription factor-1 (TTF-1), also known as Nkx2.1
, contributed substantially to the regulation of SP-A expression in ATII cells [12-14].
A minor alteration in transcription in homeobox genes Nkx2.1
has been hypothesized as one possible mechanism of familial CLE ; however a literature search to relate Nkx2.1
with gene defects seen in WBS did not reveal any associations.
However, the etiology of TD is still unclear but can be explained on a small scale by genetic mutations in 4 transcription factors (FOXE1 , NKX2.1
, PAX8 [7, 8], and NKX2.5 ) and at the thyrotrophin receptor , which are genes important in the development and normal function of the thyroid gland [11-13].
miRNA miR function Regulation miR-16 p53, cell cycle, JAK/STAT signaling Down miR-21 Fatty acid synthesis, apoptosis miR-146a Inflammation, NF[kappa][beta] mediator miR-223 Immunology Up miR-129 Cell cycle regulation, apoptosis Down miR-634 Inflammation miR-340 Cell migration and invasion Up miR-365 Targets NKX2.1
miR-143 Cardiogenesis Down miR-21 Fatty acid biosynthesis, apoptosis Up Let-7c Cell proliferation, angiogenesis Down miR-146a Inflammation, NF[kappa][beta] mediator miR-150 Hematopoeiesis miR-203 DNA damage response miR-340 Cell migration and invasion miR-443 Unknown miR-223 Immunology Down miR-29b Apoptosis Up RNU6-2 Reference miR miRNA Tissue/cell type Source miR-16 Placenta Maccani et al.
For example, in pluripotent embryonic stem cells (which can differentiate into any cell type) the neural precursor genes Dlx2, Handl, Msx2, Nestin, Nkx2.1
, Nkx2.2, Olig2, Pax6, and Sox1 all are bivalently marked, whereas in multipotent, neural precursor cells (which only can develop further into different types of neurons) only Dlx2 and Pax6 maintain this conformation.
In models of lung adenocarcinoma, the researchers uncovered a set of elevated proteins that are regulated by the NKX2.1
transcription factor, which has been linked to lung development and function.
Thyroid transcription factor 1, also named NKX2 homeobox 1 (NKX2.1
), is a nuclear protein, approximately 38 kDa, composed of a single polypeptide of 371 amino acids belonging to the family of homeodomain transcription factors.
Mice deficient in Shh or RA or that lack Nkx2.1
, the gene for a transcription factor active in early lung development [also called thyroid transcription factor 1 (Ttf1)], develop an incomplete separation of the foregut and trachea known as a tracheoesophageal fistula (Litingtung et al.
expression, nuclear pattern, prostate adenocarcinoma (hematoxylin-eosin, original magnification X10 [A]; original magnification X10 [B]).