The Chronobiology Laboratory



Building 8, Laboratory 1.15

Department of Biomedical Sciences and Medicine.

University of Algarve

Phone: +351 289 244 589

Team Members

Isabel Palmeirim  (Principal Investigator)

Ana Mesquita (Post Doctoral Researcher)

Tomás Pais de Azevedo (PhD Student)

Alexandra Filipe (PhD Student)

Ramiro Magno (PhD Student)

About the CRL

The Chronobiology Laboratory (CBL) is focused on addressing how is time controlled during embryonic development. The CBL group provided the first molecular evidence for the existence of a molecular clock underlying an embryonic process. Subsequently the CBL group has demonstrated that this molecular clock is providing the cell temporal and positional information in at least two embryonic dimensions. Furthermore the OL group identified the first left-sided expressed gene that links left-right patterning with bilateral synchronization of the segmentation clock, evidencing for the first time that symmetry is not a default stage in the chick embryo. Currently the CBL is investigating the existence of a limb molecular clock and ellucidating that the temporal control exerted by cyclic gene expression is a widespread mechanism in vertebrate embryonic development. In a collaborative project, the CBL unit is redefining the role of the ectoderm in somitogenesis. The CBL is actively screening for Hairy1 (a clock gene) protein partners. The CBL unit has demonstrated that notochord-derived signaling is required for timely somite segmentation and for the pacing of the molecular clock. The CBL unit is also actively characterizing circadian gene expression during early development. Overall, the aim of the OL unit is to understand the temporal and spatial integration of molecular clocks during development.

Publications (2008-2014)

1.    Magno R, Duarte, I, Andrade, RP, Palmeirim, I. rdml: A Mathematica package for parsing and importing Real-Time qPCR data. BMC Research Notes. 2017; 10:208.

Magno R, Andrade RP, Palmeirim I. RDML Importer: Real-Time qPCR Data Markup Language importer. The Mathematica Journal (manuscript accepted for publication).

2.     Sheeba CJ, Andrade RP, Palmeirim I. Mechanisms of vertebrate embryo segmentation: Common themes in trunk and limb development. Seminars in Cell and Developmental Biology, 2016 Jan 19. pii: S1084-9521(16)30010-6. doi: 10.1016/j.semcdb.2016.01.010.

3.     Sheeba CJ, Andrade RP, Palmeirim I. Getting a handle on embryo limb development: Molecular interactions driving limb outgrowth and patterning. Seminars in Cell and Developmental Biology, DOI information: 10.1016/j.semcdb.2015.01.007

4.     Gouveia A, Marcelino HM, Gonçalves L, Palmeirim I and Andrade RP – Patterning in Time and Space: HoxB Cluster gene expression in the developing chick embryo. Cell Cycle. 2015 Jan 2;14(1):135-145. DOI: 10.4161/15384101.2014.972868

5.     Resende T, Andrade RP, Palmeirim I., Timing Embryo Segmentation: Dynamics and Regulatory Mechanisms of the Vertebrate Segmentation Clock. BioMed Research International, vol. 2014, Article ID 718683, 12 pages, 2014. doi:10.1155/2014/718683.

6.     Monteiro AS, Freitas R., Palmeirim I. Genomics of zebrafish hoxba and hoxbb loci. J. Applied Ichthyology. 2014August 30(4): 597-840.

7.     Sheeba CJ, Andrade RP, Palmeirim I. Limb patterning: from signalling gradients to molecular oscillations. 2014. J.  Mol. Biol. DOI 10.1016/j.jmb.2013.11.022

8.     Miranda-Gonçalves V, Honavar M, Pinheiro C, Martinho O, Pires MM, Pinheiro C, Cordeiro M, Bebiano G, Costa P, Palmeirim I, Reis RM, Baltazar F. Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets. Neuro Oncol. 2013 Feb; 15(2):172-88; IF = 5,723;

9.     Sheeba CJ, Andrade RP and Palmeirim I. Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb. Biology Open. 2012 Nov 15;1(11):1102-10.

10.  Sheeba CJ, Palmeirim I, Andrade RP. Retinoic acid signaling regulates embryonic clock hairy2 gene expression in the developing chick limb. Biochem Biophys Res Commun. 2012 Jul 13;423(4):889-94. ] IF = 2,484;

11.  Gonçalves L, Vinhas M, Pereira R, Pais de Azevedo T, Bajanca F and Palmeirim I. Circadian Clock genes Bmal1 and Clock during early chick development Dev Dyn. 2012 Aug;241(8):1365-73. IF =3,018;

12.  Pais de Azevedo T, Zuzarte-Luís V, Gonçalves L, Marques C, Palmeirim I. Tissue regulation of somitic colloid-like1 gene expression. Biochem Biophys Res Commun. 2012 Jul 27;424(2):295-300.  IF = 2,484;

13.  Azevedo M.-M, Fonseca F, Andrade RP, Palmeirim I. The impact of alternative science education methodologies on the motivation and acquisition of scientific concepts. Education Research Journal Vol. 2(5): 132- 137, May 2012;

14.  Azevedo M, Fonseca F, Teixeira A, Brito C, Andrade RP, Palmeirim I. 2011. The impact of experimental activities on the motivation and acquisition of scientific concepts at the basic school level. Education Research Journal Vol. 2(2): 30-36, February 2012;

15.  Pais-de-Azevedo T, Witten P. E., Huysseune A, Bensimon-Brito A, Winkler C, To T.T., Palmeirim I. Interrelationship and modularity of notochord and somites: A comparative view on zebrafish and chicken vertebral body development. Journal of Applied Ichthyology Journal of Applied Ichthyology, 2012 Jun;Vol. 28, SI3; 316-319; IF = 0,869, Cit=2;

16.  Resende TP, Ferreira M, Tavares AT, Teillet M-A, Andrade RP and Palmeirim I. Sonic hedgehog in temporal control of somite formation. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12907-12. Epub 2010 Jul 1.

17.  Sheeba CJ, Andrade RP, Palmeirim I. Comprehensive analysis of fibroblast growth factor receptor expression pattern during chick forelimb development, Int J Dev Biol. 2010;54(10):1517-26.

18.  Martins GG, Rifes P, Amândio R, Rodrigues G, Palmeirim I and Thorsteinsdóttir S. Dynamic 3D Cell Rearrangements Guided by a Fibronectin Matrix Underlie Somitogenesis, Plos One, 2009 Oct 15;4(10):e7429.

19.  Leitner, M., Castanheira, J., Ferreira, L., Ferreira, M., Palmeirim, I., Rosa, C.C., Podoleanu, A.G.In-vivo in situ en-face optical coherence tomography imaging of chick embryos. Proc. SPIE 7372, Optical Coherence Tomography and Coherence Techniques IV, 73720Y (July 13, 2009); doi:10.1117/12.831859

20.  Palmerim I and Aréchaga J. A small great history of the sister Societies of Developmental Biology in Spain and Portugal, International Journal of Developmental Biology, Int J Dev Biol. 2009;53(8-10):1261-8.

21.  Osório L, Teillet M-A, Palmeirim I, Catala M. (2009) Neural crest ontogeny during secondary neurulation: a gene expression pattern study in the chick embryo, International Journal of Developmental Biology, 2009;53(4):641-8.

22.  Pascoal S and Palmeirim I. (2009) Portuguese contributions to the embryonic molecular clock discovery and characterization. Int J Dev Biol. 2009;53(8-10):1421-6.

23.  Rifes P, Carvalho L, Lopes C, Andrade RP, Rodrigues G, Palmeirim I and Thorsteinsdóttir S. (2007) Redefining the role of ectoderm in somitogenesis: a player in the formation of the fibronectin matrix of presomitic mesoderm, Development, 134(17):3155-65.

24.  Sheeba CJ, Palmeirim I. Andrade RP. (2007) Chick Hairy1 protein interacts with Sap18, a component of the Sin3/HDAC transcriptional repressor complex, BMC Developmental Biology, Jul 10;7:83.

25.  Andrade RP, Palmeirim I, Bajanca F. (2007) Molecular Clocks Underlying Vertebrate Embryo Segmentation: a Ten-Year-Old hairy-Go-Round. Birth Defects Res C Embryo Today, Jun 28;81(2):65-83.

26.  Pascoal S and Palmeirim I. (2007) Watch-ing out for chick limb development. Integrative and Comparative Biology, 47-3:382-389.

27.  Pascoal S, Carvalho CR, Rodriguez-León J, Delphini MC, Duprez D, Thorsteinsdóttir S and Palmeirim I (2007) A molecular clock operates during chick autopod proximal-distal outgrowth. Journal of Molecular Biology, Apr 27;368(2):303-9.

28.  Pascoal S, Andrade RP, Bajanca F and Palmeirim I. (2007) Progressive mRNA decay establishes an mkp3 expression gradient in the chick limb bud. Biochemical and Biophysical Research Communications, 352: 153-157.

29.  Rodrigues S, Santos J, Palmeirim I. (2006) Molecular characterization of the rostral-most somites in early somitic stages of the chick embryo. Gene expression patterns, Feb; 16;

30.  Stern CD, Charité J, Deschamps J, Duboule D, Durston AJ, Kmita M, Nicolas J-F, Palmeirim I, Smith JC and Wolpert L. (2006) Head-tail patterning of the vertebrate embryo: one, two or many unresolved problems? International Journal of Developmental Biology, 50(1):3-15;

31.  Saúde L, Lourenço R, Gonçalves A and Palmeirim I. (2005). terra is a left-right asymmetry gene required for left-right synchronization of the segmentation clock,  Nature Cell Biology, Sep; 7(9): 918-20

32.  Andrade R, Pascoal S, Palmeirim I. (2005). Thinking Clockwise. Brain Research Reviews, Sep; 49(2):114-9.

33.  Freitas C, Rodrigues S, Saúde L and Palmeirim I. (2005). Running after the clock. International Journal of Developmental Biology, 49(2-3): 317-24;

34.  Freitas C, Rodrigues S, Charrier J-B, Teillet M-A and Palmeirim I. (2002). Horloge moléculaire et segmentation des vertébrés: qui fait quoi?  Médecine et Sciences, 18: 883-7;

35.  Freitas C, Rodrigues S, Charrier J-B, Teillet M-A and Palmeirim I. (2001). Evidence for medial/lateral specification and positional information within the presomitic mesoderm. Development, 128 (24): 5139-5147;

36.  Jouve C, Palmeirim I, Henrique D, Johannes B, Gossler A, Ish-Horowicz D and Pourquié O. (2000) – Notch signalling is required to maintain the vertebrate segmentation clock  -Development 127 (7), 1421-9;

37.  Palmeirim I. (1999) – La segmentation chez les vertébrés: Une horloge meléculaire liée à la segmentation périodique des somites – Journal de la Société de Biologie 193 (1), 243-256;

38.  Palmeirim I, Dubrulle J, Henrique D and Pourquié O.(1998) – Uncoupling segmentation and somitogenesis in the chick presomitic mesoderm – Developmental genetics 23, 77-85;

39.  Pourquié O and Palmeirim I. (1998) – Une horloge moléculaire liée à la segmentation des vertébrés – Médecine Sciences 3, 340-343;

40.  Palmeirim I, Henrique D, Ish-Horowicz D and Pourquié O. (1997) – Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis – Cell 91, 639-648.

Papers in National Journals:

  1. Pascoal S and Palmeirim I. (2006) Desenvolvimento embrionário dos membros dos vertebrados e suas malformações congénitas. Acta Pediatr Port, 37(5):200-4
  2. Osório L and Palmeirim I. Malformações no desenvolvimento embrionário da coluna vertebral: a importância do relógio molecular. Viver Saúde, 1: 14-20 (2006);


  1. Palmeirim I and Manaia A. (2005) – Translation of the book “Quimeras, clones e genes” from Nicole Le Douarin, Edition of Fundação Calouste Gulbenkian;

Book sections:

  1. Palmeirim I, Rodrigues S, Dale JK, and Maroto M.  (2008) Development on time. In: “Cellular oscillatory mechanisms”, Landes Bioscience Publishers, Adv Exp Med Biol. 2008; 641: 62-71.
  2. Martins GG, Rifes P, Amândio R, Campinho P, Palmeirim I and Thorsteinsdóttir S. 3D visualization and analysis of cell-matrix transformations in whole-mount and live embryos using confocal and multi-photon microscopy. In: “Modern Research and Educational Topics in Microscopy”, Vol I, pp. 426-433.
  3. Raquel P. Andrade and Isabel Palmeirim. (2007). “Desenvolvimento Embrionário: Uma Questão de RNA”. In O Mundo do RNA: Novos desafios e Perspectivas Futuras. Edited by Cecília M. Arraiano and Arsénio M. Fialho, Lidel-Edições Técnicas, Lda., pp. 141-154.

Team Members


Representative Image


Project Grants

FCT research projects:

Human Mesenchymal Stem Cells Chronobiology: evaluating the crosstalk between the Embryonic and Circadian Clocks – PTDC/BIM-MED/1063/2012

Molecular parallelisms in vertebrate somitogenesis and limb development – PTDC/SAU-OBD/099758/2008.

The role of molecular clock genes in temporal control of mesoderm patterning in vertebrate embryos – PTDC/SAU-OBD/105111/2008.

Identification of molecular interactions in the chick “segmentation clock” using the yeast One-hybrid and Two-hybrid approaches – POCI/BIA-BCM/62688/2004.

EMBO Small Grants Scheme for initiatives in Science & Society.

New aspects on coordinating limb bud development – POCTI/BCI/42040/2001

Time counting system during vertebrate embryonic development – POCTI/1999/BCI/34599.

European research projects:

April 2004 to Mars 2009- Member of the Network of excellence “Cells into organs” EU/FP6 Cells into Organs: Functional genomics for development and disease of mesodermal organ systems ( Coordinator of the “Workpackage: Vertebrate somitogenesis” from this European Network of Excelence;

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