K12 Limbs

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Limbs - Arms and Legs

Appendicular skeleton
K12 Links: Start Here | Week 1 | Week 2 | Week 3 | Week 4 | Week 5 to 8 | Arms and Legs | Heart | Fetus | Brain Growth | Eyes and Ears | Animal Development Times | Humans and Animal Embryology | Comparative Embryology | Thalidomide

The arms and legs (we call them "limbs") begin as small buds on the sides of the embryo body. This page will describe the genes associated with limb development. What we now know is that the same patterning genes are used by all animals that form limbs.

Many of these patterning genes are "transcription factors", that is they are molecular switches that can turn on families of other genes in the cell associated with that developmental process. Pattern signalling occurs before we see the limb features develop.

Human Limb Development during week 6

Stage16-17-limbs01.jpg

Human Limb Development during week 8

Stage20-23 limbs a.jpg

From week 5 to week 8 of development, changes occur in the shape and structure of the embryo limbs. In humans by the end of this time the basic limb structure has been formed, most of the rest of prenatal growth is an increase in size.

The arms begin to develop before the legs. If you look at the whole embryo the legs always look younger (less developed) than the arms (almost a stage behind, about 2 days difference).

The same upper before lower is seen in the mouse and other species.

Mouse limb skeleton cartoon.jpg

Now look above at the human limb and see what changes you can see in the shape, features and position of the arm and leg.

Towards the end of this time (9 weeks) the embryo will also begin to move the arms and legs.

Limb Pattern Gene Evolution

A good example of how patterning has been conserved between animals can be shown with the fly.

If there is a mutation in the Hox gene (determining leg position) then the abnormal fly forms a limb where the antenna should be, as shown below.

Fly wild-type head.jpg Fly antennapedia head.jpg
Normal fly head with antenna Abnormal fly head with legs for antenna

The same Hox genes have been identified as controlling limb position for vertebrate animals.


Limb Position

Positioning of where the limbs will be along the length of the embryo is determined by the specific expression of Homeobox (Hox) genes.

This can turn on growth factor expression (Fibroblast growth factor, FGF) that leads to the local growth of the limb in the embryo.

Experimentally this has been shown in chickens by implanting beads that release growth factors. This changes the position or pattern of the developing limb.

Limb Identity

Whether an upper (arm) or lower (leg) will form at that location is controlled local expression of T-box (Tbx) genes.

Mouse embryo limb Tbx (blue) Expression

Limb patterning factors 09.jpg

  • Tbx5 - upper limb.
  • Tbx4 - lower limb.
  • Tbx2 and Tbx3 - both limbs.

Limb Pattern

Inside both the upper and lower limb similar patterning mechanisms are then used to form the 3 dimensional (3D) structure of the limb. This patterning in all animals has the same genetic controls expressed in localised regions of the developing limb.

This "patterning" forms the 3 main axes of the limb.

Axis Proximodistal Dorsoventral Anteroposterior
Limb Structure shoulder to fingers, hip to toes back and front of the limb order of digits
Gene Wnt7a growth factor then secretes other growth factors (FGF2, 4, 8) BMP growth factor Sonic hedgehog (SHH)
Where tip of the limb Apical Ectodermal Ridge (AER) back of the limb mesenchyme Zone of Polarizing Activity (ZPA)
Expression Example
(mouse)
Limb patterning factors 04.jpg Limb patterning factors 01.jpg Limb patterning factors 03.jpg

Different Species Limbs

Different animal species make different types of limbs with the same signals. You can see this in the pattern of bones forming the skeleton of the limb.

Limb comparison cartoon

When Limb Patterning Goes Wrong

ZPA abnormality in this cat leads to additional digits (polydactyl).

Cat 6 toes.jpg

Words Used

arm - the upper limb or in animals the forelimb. (In anatomy, this is only the part between shoulder and elbow)

digit - word used to describe either the finger or toe.

leg - the upper limb or in animals the hindlimb. (In anatomy, this is only the part between hip and knee)

limb - word used to describe either the arm or leg.

limb bud - the first time you can see on the embryo surface where the arm or leg will form. It looks like a "bud" or "paddle" without any features.

Links

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Cite this page: Hill, M.A. (2019, July 21) Embryology K12 Limbs. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/K12_Limbs

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G