From zebrafish to human: A comparative approach to elucidate the role of the thyroid hormone transporter MCT8 during brain development

被引:24
作者
Vancamp, Pieter [1 ]
Darras, Veerle M. [1 ]
机构
[1] Katholieke Univ Leuven, Dept Biol, Lab Comparat Endocrinol, B-3000 Leuven, Belgium
关键词
Thyroid hormone; MCT8; Brain development; Animal model; AHDS; CEREBELLAR PURKINJE-CELL; HERNDON-DUDLEY-SYNDROME; BLOOD-BRAIN; MONOCARBOXYLATE TRANSPORTER-8; PSYCHOMOTOR RETARDATION; FUNCTIONAL-CHARACTERIZATION; CEREBRAL-CORTEX; HYPOMYELINATING LEUKODYSTROPHIES; TRIIODOTHYROACETIC ACID; NEUROSCIENCE RESEARCH;
D O I
10.1016/j.ygcen.2017.11.023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Monocarboxylate transporter 8 (MCT8) facilitates transmembrane transport of thyroid hormones (THs) ensuring their action on gene expression during vertebrate neurodevelopment. A loss of MCT8 in humans results in severe psychomotor deficits associated with the Allan-Herndon-Dudley Syndrome (AHDS). However, where and when exactly a lack of MCT8 causes the neurological manifestations remains unclear because of the varying expression pattern of MCT8 between specific brain regions and cells. Here, we elaborate on the animal models that have been generated to elucidate the mechanisms underlying MCT8-deficient brain development. The absence of a clear neurological phenotype in Mct8 knockout mice made it clear that a single species would not suffice. The evolutionary conservation of TH action on neurodevelopment as well as the components regulating TH signalling however offers the opportunity to answer different aspects of MCT8 function in brain development using different vertebrate species. Moreover, the plethora of tools for genome editing available today facilitates gene silencing in these animals as well. Studies in the recently generated mct8-deficient zebrafish and Mct8/Oatp1c1 double knockout mice have put forward the current paradigm of impaired TH uptake at the level of the blood-brain barrier during peri- and postnatal development as being the main pathophysiological mechanism of ANDS. RNAi vector-based, cell-specific induction of MCT8 knockdown in the chicken embryo points to an additional function of MCT8 at the level of the neural progenitors during early brain development. Future studies including also additional in vivo models like Xenopus or in vitro approaches such as induced pluripotent stem cells will continue to help unravelling the exact role of MCT8 in developmental events. In the end, this multispecies approach will lead to a unifying thesis regarding the cellular and molecular mechanisms responsible for the neurological phenotype in AHDS patients. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:219 / 229
页数:11
相关论文
共 138 条
[1]  
Allan W, 1944, AM J MENT DEF, V48, P325
[2]   Identification and Functional Characterization of Zebrafish Solute Carrier Slc16a2 (Mct8) as a Thyroid Hormone Membrane Transporter [J].
Arjona, Francisco J. ;
de Vrieze, Erik ;
Visser, Theo J. ;
Flik, Gert ;
Klaren, Peter H. M. .
ENDOCRINOLOGY, 2011, 152 (12) :5065-5073
[3]   Prenatal diagnosis of thyroid hormone resistance [J].
Asteria, C ;
Rajanayagam, O ;
Collingwood, TN ;
Persani, L ;
Romoli, R ;
Mannavola, D ;
Zamperini, P ;
Buzi, F ;
Ciralli, F ;
Chatterjee, VKK ;
Beck-Peccoz, P .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (02) :405-410
[4]   The zebrafish genome editing toolkit [J].
Ata, H. ;
Clark, K. J. ;
Ekker, S. C. .
ZEBRAFISH: GENETICS, GENOMICS, AND TRANSCRIPTOMICS, 4TH EDITION, 2016, 135 :149-170
[5]   Brain Meets Body: The Blood-Brain Barrier as an Endocrine Interface [J].
Banks, William A. .
ENDOCRINOLOGY, 2012, 153 (09) :4111-4119
[6]   Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development [J].
Barez-Lopez, Soledad ;
Jesus Obregon, Maria ;
Bernal, Juan ;
Guadano-Ferraz, Ana .
CEREBRAL CORTEX, 2018, 28 (05) :1783-1793
[7]   Effect of Triiodothyroacetic Acid Treatment in Mct8 Deficiency: A Word of Caution [J].
Barez-Lopez, Soledad ;
Jesus Obregon, Maria ;
Martinez-de-Mena, Raquel ;
Bernal, Juan ;
Guadano-Ferraz, Ana ;
Morte, Beatriz .
THYROID, 2016, 26 (05) :618-626
[8]  
BARRES BA, 1994, DEVELOPMENT, V120, P1097
[9]   SUCCESSFUL TREATMENT OF HYPERTHYROIDISM DUE TO NON-NEOPLASTIC PITUITARY TSH HYPERSECRETION WITH 3,5,3'-TRIIODOTHYROACETIC ACID (TRIAC) [J].
BECKPECCOZ, P ;
PISCITELLI, G ;
CATTANEO, MG ;
FAGLIA, G .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 1983, 6 (03) :217-223
[10]   Lessons from morpholino-based screening in zebrafish [J].
Bedell, Victoria M. ;
Westcot, Stephanie E. ;
Ekker, Stephen C. .
BRIEFINGS IN FUNCTIONAL GENOMICS, 2011, 10 (04) :181-188